DOI QR코드

DOI QR Code

VEGF-VEGFR Signals in Health and Disease

  • 투고 : 2013.12.30
  • 심사 : 2014.01.15
  • 발행 : 2014.01.31

초록

Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.

키워드

참고문헌

  1. Alitalo, K. and Carmeliet, P. (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1, 219-227. https://doi.org/10.1016/S1535-6108(02)00051-X
  2. Ambati, B. K., Nozaki, M., Singh, N., Takeda, A., Jani, P. D., Suthar, T., Albuquerque, R. J., Richter, E., Sakurai, E., Newcomb, M. T., Kleinman, M. E., Caldwell, R. B., Lin, Q., Ogura, Y., Orecchia, A., Samuelson, D. A., Agnew, D. W., St Leger, J., Green, W. R., Mahasreshti, P. J., Curiel, D. T., Kwan, D., Marsh, H., Ikeda S, Leiper, L. J., Collinson, J. M., Bogdanovich, S., Khurana, T. S., Shibuya, M., Baldwin, M. E., Ferrara, N., Gerber, H. P., De Falco, S., Witta, J., Baffi, J. Z., Raisler, B. J. and Ambati, J. (2006) Corneal avascularity is due to soluble VEGF receptor-1. Nature 443, 993-997. https://doi.org/10.1038/nature05249
  3. Barleon, B., Sozzani, S., Zhou, D., Weich, H. A., Martovani, A. and Marme, D. (1996) Migration of human monocytes in response to vascular endothelilal growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87, 3336-3343.
  4. Beck, H., Raab, S., Copanaki, E., Heil, M., Scholz, A., Shibuya, M., Deller, T., Machein, M. and Plate, K. H. (2010) VEGFR-1 signaling regulates the homing of bone marrow derived cells in a mouse stroke model. J. Neuropathol. Exp. Neurol. 69,168-175. https://doi.org/10.1097/NEN.0b013e3181c9c05b
  5. Bellomo, D., Headrick, J. P., Silins, G. U., Paterson, C. A., Thomas, P. S., Gartside, M., Mould, A., Cahill, M. M., Tonks, I. D., Grimmond, S. M., Townson, S., Wells, C., Little, M., Cummings, M. C., Hayward, N. K. and Kay, G. F. (2000) Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia. Circ. Res. 86, E29-35. https://doi.org/10.1161/01.RES.86.2.e29
  6. Bry, M., Kivela, R., Holopainen, T., Anisimov, A., Tammela, T., Soronen, J., Silvola, J., Saraste, A., Jeltsch, M., Korpisalo, P., Carmeliet, P., Lemstrom, K. B., Shibuya, M., Yla-Herttuala, S., Alhonen, L., Mervaala, E., Andersson, L. C., Knuuti, J. and Alitalo, K. (2010) Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation. Circulation 122,1725-1733. https://doi.org/10.1161/CIRCULATIONAHA.110.957332
  7. Carmellet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kleckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., Declercq, C., Pawlling, J., Moons, L., Collen, D., Risau, W. and Nagy, A. (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435-439. https://doi.org/10.1038/380435a0
  8. Clauss, M., Weich, H., Breier, G., Knies, U., Rockl, W., Waltenberger, J. and Risau, W. (1996) The vascular endothelial growth factor receptor Flt-1 mediates biological activities. J. Biol. Chem. 271, 17629-17634. https://doi.org/10.1074/jbc.271.30.17629
  9. Cohen, M. H., Gootenberg, J., Keegan, P. and Pazdur, R. (2007) FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 12, 713-718. https://doi.org/10.1634/theoncologist.12-6-713
  10. De Vries, C., Escobedo, J. A., Ueno, H., Houck, K., Ferrara, N. and Williams, L. T. (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255, 989-991 https://doi.org/10.1126/science.1312256
  11. Dhondt, J., Peeraer, E., Verheyen, A., Nuydens, R., Buysschaert, I., Poesen, K., Van Geyte, K., Beerens, M., Shibuya, M., Haigh, J. J., Meert, T., Carmeliet, P. and Lambrechts, D. (2011) Neuronal FLT1 receptor and its selective ligand VEGF-B protect against retrograde degeneration of sensory neurons. FASEB J. 25, 1461-1473. https://doi.org/10.1096/fj.10-170944
  12. Dias, S., Shmelkov, S. V., Lam, G. and Rafii S. (2002) VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood 99, 2532-2540. https://doi.org/10.1182/blood.V99.7.2532
  13. Dumont, D. J., Jussila, L., Taipale, J., Lymboussaki, A., Mustonen, T., Pajusola, K., Breitman, M. and Alitalo, K. (1998) Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282, 946-949. https://doi.org/10.1126/science.282.5390.946
  14. Dvorak, H. F. (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J. Clin. Oncol. 20, 4368-4380. https://doi.org/10.1200/JCO.2002.10.088
  15. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K. S., Powell-Braxton, L., Hillan, K. J. and Moore, M. W. (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380, 439-442. https://doi.org/10.1038/380439a0
  16. Ferrara, N. (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25, 581-611. https://doi.org/10.1210/er.2003-0027
  17. Foidart, J. M., Schaaps, J. P., Chantraine, F., Munaut, C. and Lorquet, S. (2009) Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia-a step forward but not the definitive answer. J. Reprod. Immunol. 82, 106-111. https://doi.org/10.1016/j.jri.2009.09.001
  18. Fong, G. H., Rossant, J., Gertsentein, M. and Breitman, M. L. (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376, 66-70. https://doi.org/10.1038/376066a0
  19. Freitas, C., Larrivee, B. and Eichmann, A. (2008) Netrins and UNC5 receptors in angiogenesis. Angiogenesis 11, 23-29. https://doi.org/10.1007/s10456-008-9096-2
  20. Gilbert, J. S., Babcock, S. A. and Granger, J. P. (2007) Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble Fms-like tyrosine kinase-1 expression. Hypertension 50, 1142-1147. https://doi.org/10.1161/HYPERTENSIONAHA.107.096594
  21. Hanahan, D. and Folkman, J. (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353-364. https://doi.org/10.1016/S0092-8674(00)80108-7
  22. Heldin, C. H. and Westermark, B. (1999) Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79, 1283-1316. https://doi.org/10.1152/physrev.1999.79.4.1283
  23. Hida, K., Ohga, N., Akiyama, K., Maishi, N. and Hida, Y. (2013) Heterogeneity of tumor endothelial cells. Cancer Sci. Aug 12. doi: 10.1111/cas.12251. [Epub ahead of print]
  24. Hiratsuka, S., Minowa, O., Kuno, J., Noda, T. and Shibuya, M. (1998) Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc. Natl. Acad. Sci. U.S.A. 95, 9349-9354. https://doi.org/10.1073/pnas.95.16.9349
  25. Hiratsuka, S., Nakamura, K., Iwai, S., Murakami, M., Itoh, T., Kijima, H., Shipley, J. M., Senior, R. M. and Shibuya, M. (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung specific metastasis. Cancer Cell 2, 289-300. https://doi.org/10.1016/S1535-6108(02)00153-8
  26. Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., Ferrara, N., Fyfe, G., Rogers, B., Ross, R. and Kabbinavar, F. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335-2342. https://doi.org/10.1056/NEJMoa032691
  27. Huveldt, D., Lewis-Tuffin, L. J., Carlson, B. L., Schroeder, M. A., Rodriguez, F., Giannini, C., Galanis, E., Sarkaria, J. N. and Anastasiadis, P. Z. (2013) Targeting Src family kinases inhibits bevacizumab-induced glioma cell invasion. PLoS One. 8, e56505. https://doi.org/10.1371/journal.pone.0056505
  28. Jin, J., Sison, K., Li, C., Tian, R., Wnuk, M., Sung, H. K., Jeansson, M., Zhang, C., Tucholska, M., Jones, N., Kerjaschki, D., Shibuya, M., Fantus, I. G., Nagy, A., Gerber, H. P., Ferrara, N., Pawson, T., and Quaggin, S. E. (2012) Soluble FLT1 binds lipid microdomains in podocytes to control cell morphology and glomerular barrier function. Cell 151, 384-399. https://doi.org/10.1016/j.cell.2012.08.037
  29. Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., Zhu, Z., Hicklin, D., Wu, Y., Port, J. L., Altorki, N., Port, E. R., Ruggero, D., Shmelkov, S. V., Jensen, K. K., Rafii, S. and Lyden, D. (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820-827. https://doi.org/10.1038/nature04186
  30. Kato, T., Ito, Y., Hosono, K., Suzsuki, T., Tamaki, H., Minamino, T., Kato, S., Sakagami, H., Shibuya, M. and Majima, M. (2011) Vascular endothelial growth factor receptor-1 signaling promotes liver repair through restoration of liver microvasculature after acetaminophen hepatotoxicity. Toxicol. Sci. 120, 218-229. https://doi.org/10.1093/toxsci/kfq366
  31. Kendall, R. L. and Thomas, K. A. (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Natl. Acad. Sci. U.S.A. 90, 10705-10709. https://doi.org/10.1073/pnas.90.22.10705
  32. Kerber, M., Reiss, Y., Wickersheim, A., Jugold, M., Kiessling, F., Heil, M., Tchaikovski, V., Waltenberger, J., Shibuya, M., Plate, K.H. and Machein, M.R. (2008) Flt-1 signaling in macrophages promotes glioma growth in vivo. Cancer Res. 68, 7342-7351. https://doi.org/10.1158/0008-5472.CAN-07-6241
  33. Keyt, B. A., Nguyen, H. V., Berleau, L. T., Duarte, C. M., Park, J., Chen, H. and Ferrara, N. (1996) Identification of vascular endothelial growth factor determinanats for binding KDR and FLT-1 receptors. Generation of receptor-selective VEGF variants by site-directed mutagenesis. J. Biol. Chem. 271, 5638-5646. https://doi.org/10.1074/jbc.271.10.5638
  34. Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S. and Ferrara, N. (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362, 841-844. https://doi.org/10.1038/362841a0
  35. Kim, M., Park, H. J., Seol, J. W., Jang, J. Y., Cho, Y. S., Kim, K. R., Choi, Y., Lydon, J. P., Demayo, F. J., Shibuya, M., Ferrara, N., Sung, H. K., Nagy, A., Alitalo, K. and Koh, G. Y. (2013) VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodeling during pregnancy. EMBO Mol. Med. 5, 1415-1430. https://doi.org/10.1002/emmm.201302618
  36. Koga, K., Osuga, Y., Yoshino, O., Hirota, Y., Ruimeng, X., Hirata, T., Takeda, S., Yano, T., Tsutsumi, O. and Taketani, Y. (2003) Elevated serum soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) levels in women with preeclampsia. J. Clin. Endocrinol. Metab. 88, 2348-2351. https://doi.org/10.1210/jc.2002-021942
  37. Kumasawa, K., Ikawa, M., Kidoya, H., Hasuwa, H., Saito-Fujita, T., Morioka, Y., Takakura, N., Kimura, T. and Okabe, M. (2011) Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc. Natl. Acad. Sci. U.S.A. 108, 1451-1455. https://doi.org/10.1073/pnas.1011293108
  38. Laurent, J., Hull, E. F., Touvrey, C., Kuonen, F., Lan, Q., Lorusso, G., Doucey, M. A., Ciarloni, L., Imaizumi, N., Alghisi, G.C., Fagiani, E., Zaman, K., Stupp, R., Shibuya, M., Delaloye, J. F., Christofori, G. and Ruegg, C. (2011) Proangiogenic factor PlGF programs CD11b(+) myelomonocytes in breast cancer during differentiation of their hematopoietic progenitors. Cancer Res. 71, 3781-3791. https://doi.org/10.1158/0008-5472.CAN-10-3684
  39. Leung, D. W., Cachianes, G., Kuang, W. J., Goeddel, D. V. and Ferrara, N. (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246, 1306-1309. https://doi.org/10.1126/science.2479986
  40. Levine, R. J., Maynard, S. E., Qian, C., Lim, K. H., England, L. J., Yu, K. F., Schisterman, E. F., Thadhani, R., Sachs, B. P., Epstein, F. H., Sibai, B. M., Sukhatme, V. P. and Karumanchi, S. A. (2004) Circulating angiogenic factors and the risk of preeclampsia. N. Engl. J. Med. 350, 672-683. https://doi.org/10.1056/NEJMoa031884
  41. Luo, L., Uehara, H., Zhang, X., Das, S. K., Olsen, T., Holt, D., Simonis, J. M., Jackman, K., Singh, N., Miya, T. R., Huang, W., Ahmed, F., Bastos-Carvalho, A., Le, Y. Z., Mamalis, C., Chiodo, V. A., Hauswirth, W. W., Baffi, J., Lacal, P. M., Orecchia, A., Ferrara, N., Gao, G., Young-Hee, K., Fu, Y., Owen, L., Albuquerque, R., Baehr, W., Thomas, K., Li, D. Y., Chalam, K. V., Shibuya, M., Grisanti, S., Wilson, D. J., Ambati, J. and Ambati, B. K. (2013) Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1. Elife 2:e00324.
  42. Matsumoto, T., Bohman, S., Dixelius, J., Berge, T., Dimberg, A., Magnusson, P., Wang, L., Wikner, C., Qi, J. H., Wernstedt, C., Wu, J., Bruheim, S., Mugishima, H., Mukhopadhyay, D., Spurkland, A. and Claesson-Welsh, L. (2005) VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J. 24, 2342-2353. https://doi.org/10.1038/sj.emboj.7600709
  43. Maynard, S. E., Min, J. Y., Merchan, J., Lim, K. H., Li, J., Mondal, S., Libermann, T. A., Morgan, J. P., Sellke, F. W., Stillman, I. E., Epstein, F. H., Sukhatme, V. P. and Karumanchi, S. A. (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest. 111, 649-658. https://doi.org/10.1172/JCI17189
  44. Mezquita, J., Mezquita, B., Pau, M. and Mezquita, C. (2003) Down-regulation of Flt-1 gene expression by the proteasome inhibitor MG262. J. Cell. Biochem. 89, 1138-1147. https://doi.org/10.1002/jcb.10587
  45. Minami, T., Horiuchi, K., Miura, M., Abid, M. R., Takabe, W., Noguchi, N., Kohro, T., Ge, X., Aburatani, H., Hamakubo, T., Kodama, T. and Aird, W. C. (2004) Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. J. Biol. Chem. 279, 50537-50554. https://doi.org/10.1074/jbc.M406454200
  46. Murakami, M., Iwai, S., Hiratsuka, S., Yamauchi, M., Nakamura, K., Iwakura, Y. and Shibuya, M. (2006) Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocyte/macrophages. Blood 108, 1849-1856. https://doi.org/10.1182/blood-2006-04-016030
  47. Muramatsu, M., Yamamoto, S., Osawa, T. and Shibuya, M. (2010) Vascular endothelial growth factor receptor-1 signaling promotes mobilization of macrophage lineage cells from bone marrow and stimulates solid tumor growth. Cancer Res. 70, 8211-8221. https://doi.org/10.1158/0008-5472.CAN-10-0202
  48. Nagamatsu, T., Fujii, T., Kusumi, M., Zou, L., Yamashita, T., Osuga, Y., Momoeda, M., Kozuma, S. and Taketani, Y. (2004) Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology 145, 4838-4845. https://doi.org/10.1210/en.2004-0533
  49. Niida, S., Kondo, T., Hiratsuka, S., Hayashi, S. I., Amizuka, N., Noda, T., Ikeda, K. and Shibuya, M. (2005) VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 102, 14016-14021. https://doi.org/10.1073/pnas.0503544102
  50. Noguera-Troise, I., Daly, C., Papadopoulos, N. J., Coetzee, S., Boland, P., Gale, N. W., Lin, H. C., Yancopoulos, G. D. and Thurston, G. (2006) Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 444, 1032-1037. https://doi.org/10.1038/nature05355
  51. Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Van Dorpe, J., Hellings, P., Gorselink, M., Heymans, S., Theilmeier, G., Dewerchin, M., Laudenbach, V., Vermylen, P., Raat, H., Acker, T., Vleminckx, V., Van Den Bosch, L., Cashman, N., Fujisawa, H., Drost, M. R., Sciot, R., Bruyninckx, F., Hicklin, D. J., Ince, C., Gressens, P., Lupu, F., Plate, K. H., Robberecht, W., Herbert, J. M., Collen, D. and Carmeliet, P. (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat. Genet. 28, 131-138. https://doi.org/10.1038/88842
  52. Osawa, T., Tsuchida, R., Muramatsu, M., Shimamura, T., Wang, F., Suehiro, J. I., Kanki, Y., Wada, Y., Yuasa, Y., Aburatani, H., Miyano, S., Minami, T., Kodama, T. and Shibuya, M. (2013) Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages. Cancer Res. 73, 3019-3028. https://doi.org/10.1158/0008-5472.CAN-12-3231
  53. Paez-Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Vinals, F., Inoue, M., Bergers, G., Hanahan, D. and Casanovas, O. (2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 15, 220-231. https://doi.org/10.1016/j.ccr.2009.01.027
  54. Pritchard-Jones, R. O., Dunn, D. B., Qiu, Y., Varey, A. H., Orlando, A., Rigby, H., Harper, S. J. and Bates, D. O. (2007) Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma. Br. J. Cancer 97, 223-230. https://doi.org/10.1038/sj.bjc.6603839
  55. Risau, W. (1997) Mechanisms of angiogenesis. Nature 386, 671-674. https://doi.org/10.1038/386671a0
  56. Sakurai, Y., Ohgimoto, K., Kataoka, Y., Yoshida, N. and Shibuya, M. (2005) Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc. Natl. Acad. Sci. U.S.A. 102, 1076-1081. https://doi.org/10.1073/pnas.0404984102
  57. Sallinen, H., Anttila, M., Grohn, O., Koponen, J., Hamalainen, K., Kholova, I., Kosma, V.M., Heinonen, S., Alitalo, K. and Yla-Herttuala S. (2011) Cotargeting of VEGFR-1 and -3 and angiopoietin receptor Tie2 reduces the growth of solid human ovarian cancer in mice. Cancer Gene Ther. 18, 100-109. https://doi.org/10.1038/cgt.2010.56
  58. Sase, H., Watabe, T., Kawasaki, K., Miyazono, K. and Miyazawa, K. (2009) VEGFR2-PLCgamma1 axis is essential for endothelial specification of VEGFR2+ vascular progenitor cells. J. Cell Sci. 122, 3303-3311. https://doi.org/10.1242/jcs.049908
  59. Sato, T., Amano, H., Ito, Y., Eshima, K., Minamino, T., Ae, T., Katada, C., Ohno, T., Hosono, K., Suzuki, T., Shibuya, M., Koizumi, W. and Majima M. (2013) NSAID, aspirin delays gastric ulcer healing with reduced accumulation of CXCR4+VEGFR1+ cells to the ulcer granulation tissues. Biomed Pharmacother. 67, 607-613. https://doi.org/10.1016/j.biopha.2013.01.009
  60. Sato, Y. (2013) The vasohibin family: a novel family for angiogenesis regulation. J. Biochem. 153, 5-11. https://doi.org/10.1093/jb/mvs128
  61. Sawano, A., Takahashi, T., Yamaguchi, S., Aonuma, T. and Shibuya, M. (1996) Flt-1 but not KDR/Flk-1 tyrosine kinase is a receptor for placenta growth factor (PlGF), which is related to vascular endothelial growth factor (VEGF). Cell Growth Diff. 7, 213-221.
  62. Schwartz, J. D., Rowinsky, E. K., Youssoufian, H., Pytowski, B. and Wu, Y. (2010) Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1). Cancer 116,1027-1032. https://doi.org/10.1002/cncr.24789
  63. Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X. F., Breitman, M. L. and Schuh, A. C. (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376, 62-66. https://doi.org/10.1038/376062a0
  64. Shibuya, M., Yamaguchi, S., Yamane, A., Ikeda, T., Tojo, A., Matsushime, H. and Sato, M. (1990) Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene 5, 519-524.
  65. Shibuya, M. and Claesson-Welsh, L. (2006) Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp. Cell. Res. 312, 549-560. https://doi.org/10.1016/j.yexcr.2005.11.012
  66. Shibuya, M. (2006) Vascular endothelial growth factor receptor-1 (VEGFR1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 9, 225-230 https://doi.org/10.1007/s10456-006-9055-8
  67. Shibuya, M. (2011) Involvement of Flt-1 (VEGFR-1) in cancer and preeclampsia. Proc. Jpn. Acad Ser. B. Phys. Biol. Sci. 87, 167-178. https://doi.org/10.2183/pjab.87.167
  68. Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S., Sato, T. N. and Yancopoulos, G. D. (1996) Requisite role of Angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87, 1171-1180. https://doi.org/10.1016/S0092-8674(00)81813-9
  69. Takahashi, T., Ueno, H. and Shibuya, M. (1999) VEGF activates Protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 18, 2221-2230. https://doi.org/10.1038/sj.onc.1202527
  70. Takahashi, T., Yamaguchi, S., Chida, K. and Shibuya, M. (2001) A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-${\gamma}$ and DNA synthesis in vascular endothelial cells. EMBO J. 20, 2768-2778. https://doi.org/10.1093/emboj/20.11.2768
  71. Tammela, T., Zarkada, G., Wallgard, E., Murtomaki, A., Suchting, S., Wirzenius, M., Waltari, M., Hellstrom, M., Schomber, T., Peltonen, R., Freitas, C., Duarte, A., Isoniemi, H., Laakkonen, P., Christofori, G., Yla-Herttuala, S., Shibuya, M., Pytowski, B., Eichmann, A., Betsholtz, C. and Alitalo, K. (2008) Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature 454, 656-660. https://doi.org/10.1038/nature07083
  72. Tanaka, K., Yamaguchi, S., Sawano, A. and Shibuya, M. (1997) Characterization of the extracellular domain in the vascular endothelial growth factor receptor-1 (Flt-1 tyrosine kinase). Jpn. J. Cancer Res. 88, 867-876. https://doi.org/10.1111/j.1349-7006.1997.tb00463.x
  73. Thadhani, R., Kisner, T., Hagmann, H., Bossung, V., Noack, S., Schaarschmidt, W., Jank, A., Kribs, A., Cornely, O. A., Kreyssig, C., Hemphill, L., Rigby, A. C., Khedkar, S., Lindner, T. H., Mallmann, P., Stepan, H., Karumanchi, S. A. and Benzing, T. (2011) Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia. Circulation 124, 940-950. https://doi.org/10.1161/CIRCULATIONAHA.111.034793
  74. Verheyen, A., Peeraer, E., Nuydens, R., Dhondt, J., Poesen, K., Pintelon, I., Daniels, A., Timmermans, J. P., Meert, T., Carmeliet, P. and Lambrechts, D. (2012) Systemic anti-vascular endothelial growth factor therapies induce a painful sensory neuropathy. Brain 135, 2629-2641. https://doi.org/10.1093/brain/aws145
  75. Wang, H. U., Chen, Z. F. and Anderson, D. J. (1998) Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93, 741-753. https://doi.org/10.1016/S0092-8674(00)81436-1
  76. Watnick, R. S., Cheng, Y. N., Rangarajan, A., Ince, T. A. and Weinberg, R. A. (2003) Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis. Cancer Cell 3, 219-231. https://doi.org/10.1016/S1535-6108(03)00030-8
  77. Wittko, I. M., Schanzer, A., Kuzmichev, A., Schneider, F. T., Shibuya, M., Raab, S. and Plate, K. H. (2009) VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo. J. Neurosci. 29, 8704-8714,. https://doi.org/10.1523/JNEUROSCI.5527-08.2009
  78. Xiong, Y., Huo, Y., Chen, C., Zeng, H., Lu, X., Wei, C., Ruan, C., Zhang, X., Hu, Z., Shibuya, M. and Luo, J. (2009) Vascular endothelial growth factor (VEGF) receptor-2 tyrosine 1175 signaling controls VEGF-induced von Willebrand factor release from endothelial cells via phospholipase C-gamma 1- and protein kinase A-dependent pathways. J. Biol. Chem. 284, 23217-23224. https://doi.org/10.1074/jbc.M109.019679
  79. Yamauchi, M., Imajoh-Ohmi, S. and Shibuya, M. (2007) Novel anti-angiogenic pathway of thrombospondin-1 mediated by suppression of the cell cycle. Cancer Sci. 98, 1491-1497. https://doi.org/10.1111/j.1349-7006.2007.00534.x
  80. Yan, M., Callahan, C. A., Beyer, J. C., Allamneni, K. P., Zhang, G., Ridgway, J. B., Niessen, K. and Plowman, G. D. (2010) Chronic DLL4 blockade induces vascular neoplasms. Nature 463, E6-7. https://doi.org/10.1038/nature08751
  81. Young, B. C., Levine, R. J. and Karumanchi, S. A. (2010) Pathogenesis of preeclampsia. Annu. Rev. Pathol. 5, 173-192. https://doi.org/10.1146/annurev-pathol-121808-102149

피인용 문헌

  1. Nucleoside diphosphate kinase B regulates angiogenic responses in the endothelium via caveolae formation and c-Src-mediated caveolin-1 phosphorylation vol.37, pp.7, 2017, https://doi.org/10.1177/0271678X16669365
  2. The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line vol.5, pp.6, 2015, https://doi.org/10.1016/j.apsb.2015.07.008
  3. A novel strategy to enhance angiogenesis in vivo using the small VEGF-binding peptide PR1P vol.20, pp.3, 2017, https://doi.org/10.1007/s10456-017-9556-7
  4. Effects of mesenchymal stem cells and VEGF on liver regeneration following major resection vol.401, pp.5, 2016, https://doi.org/10.1007/s00423-016-1380-9
  5. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis vol.10, pp.4, 2016, https://doi.org/10.1007/s12079-016-0352-8
  6. A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS vol.12, pp.6, 2016, https://doi.org/10.2217/fca-2016-0026
  7. Angiogenesis in glaucoma filtration surgery and neovascular glaucoma: A review vol.60, pp.6, 2015, https://doi.org/10.1016/j.survophthal.2015.04.003
  8. VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma vol.2016, 2016, https://doi.org/10.1155/2016/9607054
  9. MicroRNA-101 induces apoptosis in cisplatin-resistant gastric cancer cells by targeting VEGF-C vol.13, pp.1, 2016, https://doi.org/10.3892/mmr.2015.4560
  10. Investigation on association between five common polymorphisms in vascular endothelial growth factor and prototypes of autoimmune diseases vol.220, pp.6, 2015, https://doi.org/10.1016/j.imbio.2015.01.001
  11. Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer vol.19, pp.2, 2017, https://doi.org/10.1208/s12248-016-0015-y
  12. Ethoxyfagaronine, a synthetic analogue of fagaronine that inhibits vascular endothelial growth factor-1, as a new anti-angiogeneic agent vol.33, pp.1, 2015, https://doi.org/10.1007/s10637-014-0184-4
  13. Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction vol.12, pp.5, 2015, https://doi.org/10.3892/mmr.2015.4307
  14. Ranibizumab interacts with the VEGF-A/VEGFR-2 signaling pathway in human RPE cells at different levels vol.83, 2016, https://doi.org/10.1016/j.cyto.2016.04.014
  15. Anti-Angiogenic Effect of Metformin in Mouse Oxygen-Induced Retinopathy Is Mediated by Reducing Levels of the Vascular Endothelial Growth Factor Receptor Flk-1 vol.10, pp.3, 2015, https://doi.org/10.1371/journal.pone.0119708
  16. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism vol.7, 2016, https://doi.org/10.1038/ncomms12680
  17. Differential function and regulation of orphan nuclear receptor TR3 isoforms in endothelial cells vol.37, pp.3, 2016, https://doi.org/10.1007/s13277-015-4157-9
  18. Glutamate Neonatal Excitotoxicity Modifies VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 Protein Expression Profiles During Postnatal Development of the Cerebral Cortex and Hippocampus of Male Rats vol.63, pp.1, 2017, https://doi.org/10.1007/s12031-017-0952-7
  19. Identification of Peptidic Antagonists of Vascular Endothelial Growth Factor Receptor 1 by Scanning the Binding Epitopes of Its Ligands vol.60, pp.15, 2017, https://doi.org/10.1021/acs.jmedchem.7b00283
  20. Design and Synthesis of C-Terminal Modified Cyclic Peptides as VEGFR1 Antagonists vol.19, pp.10, 2014, https://doi.org/10.3390/molecules191015391
  21. A Novel Peptide Derived From Tissue-Type Plasminogen Activator Potently Inhibits Angiogenesis and Corneal Neovascularization vol.118, pp.5, 2017, https://doi.org/10.1002/jcb.25732
  22. Two natural eudesmane-type sesquiterpenes from Laggera alata inhibit angiogenesis and suppress breast cancer cell migration through VEGF- and Angiopoietin 2-mediated signaling pathways vol.51, pp.1, 2017, https://doi.org/10.3892/ijo.2017.4004
  23. Vascular endothelial growth factor: An important molecular target of curcumin 2017, https://doi.org/10.1080/10408398.2017.1366892
  24. Transfection of chondromodulin I into human breast cancer cells and its effect on the inhibition of cancer cell growth vol.13, pp.5, 2016, https://doi.org/10.3892/mmr.2016.5079
  25. KLF4 Promotes Angiogenesis by Activating VEGF Signaling in Human Retinal Microvascular Endothelial Cells vol.10, pp.6, 2015, https://doi.org/10.1371/journal.pone.0130341
  26. Exploring quercetin and luteolin derivatives as antiangiogenic agents vol.97, 2015, https://doi.org/10.1016/j.ejmech.2015.04.056
  27. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy vol.113, pp.15, 2016, https://doi.org/10.1073/pnas.1601649113
  28. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis vol.463, pp.4, 2015, https://doi.org/10.1016/j.bbrc.2015.05.073
  29. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation vol.5, 2014, https://doi.org/10.3389/fphar.2014.00209
  30. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy vol.17, pp.3, 2016, https://doi.org/10.2217/pgs.15.173
  31. Sulfated Hyaluronan Alters Endothelial Cell Activation in Vitro by Controlling the Biological Activity of the Angiogenic Factors Vascular Endothelial Growth Factor-A and Tissue Inhibitor of Metalloproteinase-3 vol.9, pp.11, 2017, https://doi.org/10.1021/acsami.7b01300
  32. VEGF released from a fibrin biomatrix increases VEGFR-2 expression and improves early outcome after ischaemia-reperfusion injury vol.11, pp.7, 2017, https://doi.org/10.1002/term.2114
  33. Modulation of VEGF receptor 2 signaling by protein phosphatases vol.115, 2017, https://doi.org/10.1016/j.phrs.2016.11.022
  34. Impact ofVEGFgene polymorphisms in elderly cancer patients: clinical outcome and toxicity vol.16, pp.1, 2015, https://doi.org/10.2217/pgs.14.136
  35. Ectodomain cleavage of FLT1 regulates receptor activation and function and is not required for its downstream intracellular cleavage vol.344, pp.1, 2016, https://doi.org/10.1016/j.yexcr.2016.03.020
  36. Post-transcriptional control of Amblyomin-X on secretion of vascular endothelial growth factor and expression of adhesion molecules in endothelial cells vol.101, 2015, https://doi.org/10.1016/j.toxicon.2015.04.002
  37. Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy 2017, https://doi.org/10.1073/pnas.1705066114
  38. Down-regulating HIF-1α by lentivirus-mediated shRNA for therapy of triple negative breast cancer vol.16, pp.6, 2015, https://doi.org/10.1080/15384047.2015.1040958
  39. Long-term results of pl-VEGF165 intramuscular gene transfer in patients with atherosclerotic chronic lower limb ischemia vol.8, pp.4, 2015, https://doi.org/10.17116/kardio20158443-49
  40. Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases vol.282, pp.19, 2015, https://doi.org/10.1111/febs.13342
  41. Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A vol.25, pp.2, 2017, https://doi.org/10.1016/j.str.2016.12.012
  42. Recent advances in the development of dual VEGFR and c-Met small molecule inhibitors as anticancer drugs vol.108, 2016, https://doi.org/10.1016/j.ejmech.2015.12.016
  43. Nucleoside Diphosphate Kinase B Regulates Angiogenesis Through Modulation of Vascular Endothelial Growth Factor Receptor Type 2 and Endothelial Adherens Junction Proteins vol.34, pp.10, 2014, https://doi.org/10.1161/ATVBAHA.114.304239
  44. b Modulates Endothelial VEGFR1–STAT3 Signaling Pathway and Angiogenesis in Human and Experimental Peripheral Arterial Disease vol.120, pp.2, 2017, https://doi.org/10.1161/CIRCRESAHA.116.309516
  45. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol vol.15, pp.12, 2017, https://doi.org/10.1111/ddg.13365
  46. Das infantile Hämangiom: Pathogenese und Wirkmechanismus von Propranolol vol.15, pp.12, 2017, https://doi.org/10.1111/ddg.13365_g
  47. Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00140
  48. Vascular Endothelial Growth Factor, from Basic Research to Clinical Applications vol.19, pp.12, 2018, https://doi.org/10.3390/ijms19123750
  49. Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis-mediated vascular remodeling pp.00219541, 2018, https://doi.org/10.1002/jcp.27735
  50. Rutacecarpine Inhibits Angiogenesis by Targeting the VEGFR2 and VEGFR2-Mediated Akt/mTOR/p70s6k Signaling Pathway vol.23, pp.8, 2018, https://doi.org/10.3390/molecules23082047
  51. A Subset of Paracrine Factors as Efficient Biomarkers for Predicting Vascular Regenerative Efficacy of Mesenchymal Stromal/Stem Cells pp.10665099, 2018, https://doi.org/10.1002/stem.2920
  52. Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning vol.215, pp.2, 2018, https://doi.org/10.1084/jem.20171012
  53. VEGF-A selectively inhibits FLT1 ectodomain shedding independent of receptor activation and receptor endocytosis vol.315, pp.2, 2018, https://doi.org/10.1152/ajpcell.00247.2017
  54. Characterizing Glioblastoma Heterogeneity via Single-Cell Receptor Quantification vol.6, pp.2296-4185, 2018, https://doi.org/10.3389/fbioe.2018.00092
  55. Characterization of a drug-targetable allosteric site regulating vascular endothelial growth factor signaling vol.21, pp.3, 2018, https://doi.org/10.1007/s10456-018-9606-9
  56. The urokinase plasminogen activator system components are regulated by vascular endothelial growth factor D in bovine oviduct vol.26, pp.3, 2018, https://doi.org/10.1017/S0967199418000151
  57. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis vol.35, pp.5, 2014, https://doi.org/10.1042/bsr20150171
  58. Orally Administered Mucolytic Drug l-Carbocisteine Inhibits Angiogenesis and Tumor Growth in Mice vol.354, pp.3, 2014, https://doi.org/10.1124/jpet.115.224816
  59. VASCULAR ENDOTHELIAL GROWTH FACTOR IN HEALTH AND DISEASE: A REVIEW vol.3, pp.80, 2014, https://doi.org/10.18410/jebmh/2016/929
  60. Inhibitory effect of carboplatin in combination with bevacizumab on human retinoblastoma in an in vitro and in vivo model vol.14, pp.5, 2014, https://doi.org/10.3892/ol.2017.6827
  61. Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T vol.61, pp.9, 2014, https://doi.org/10.1021/acs.jmedchem.8b00210
  62. Targeting Fluorescent Nanodiamonds to Vascular Endothelial Growth Factor Receptors in Tumor vol.30, pp.3, 2014, https://doi.org/10.1021/acs.bioconjchem.8b00803
  63. Umbilical cord blood-derived Helios-positive regulatory T cells promote angiogenesis in acute lymphoblastic leukemia in mice via CCL22 and the VEGFA-VEGFR2 pathway vol.19, pp.5, 2014, https://doi.org/10.3892/mmr.2019.10074
  64. Human Recombinant VEGFR2D4 Biochemical Characterization to Investigate Novel Anti-VEGFR2D4 Antibodies for Allosteric Targeting of VEGFR2 vol.61, pp.7, 2014, https://doi.org/10.1007/s12033-019-00181-7
  65. Anti-angiogenic activity of Gracilaria coronopifolia J.G. Agardh extract by lowering the levels of trace metals (iron, zinc and copper) in duck chorioallantoic membrane and in vitro activation of AMP- vol.46, pp.4, 2019, https://doi.org/10.1007/s11033-019-04864-x
  66. Current and Future Trends on Diagnosis and Prognosis of Glioblastoma: From Molecular Biology to Proteomics vol.8, pp.8, 2014, https://doi.org/10.3390/cells8080863
  67. 6′-Sialylgalactose inhibits vascular endothelial growth factor receptor 2-mediated angiogenesis vol.51, pp.10, 2014, https://doi.org/10.1038/s12276-019-0311-6
  68. Biochemical and Conformational Characterization of Recombinant VEGFR2 Domain 7 vol.61, pp.11, 2014, https://doi.org/10.1007/s12033-019-00211-4
  69. Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model vol.10, pp.1, 2014, https://doi.org/10.1186/s13287-019-1389-4
  70. Soluble fms-Like Tyrosine Kinase 1 Localization in Renal Biopsies of CKD vol.4, pp.12, 2014, https://doi.org/10.1016/j.ekir.2019.08.004
  71. Antiangiogenesis Potential of Alpinumisoflavone as an Inhibitor of Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) vol.16, pp.None, 2014, https://doi.org/10.2174/1573408016666200123160509
  72. Neuroprotective and Neurorestorative Effects of Epo and VEGF: Perspectives for New Therapeutic Approaches to Neurological Diseases vol.26, pp.12, 2014, https://doi.org/10.2174/1381612826666200114104342
  73. Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction vol.9, pp.5, 2014, https://doi.org/10.3390/jcm9051277
  74. Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways vol.25, pp.18, 2014, https://doi.org/10.3390/molecules25184279
  75. Modulating the Crosstalk between the Tumor and the Microenvironment Using SiRNA: A Flexible Strategy for Breast Cancer Treatment vol.12, pp.12, 2014, https://doi.org/10.3390/cancers12123744
  76. Identification of Hub Genes and Key Pathways Associated with Anti-VEGF Resistant Glioblastoma Using Gene Expression Data Analysis vol.11, pp.3, 2021, https://doi.org/10.3390/biom11030403
  77. Angiogenesis Is Differentially Modulated by Platelet-Derived Products vol.9, pp.3, 2014, https://doi.org/10.3390/biomedicines9030251
  78. Anti-VEGF agents: As appealing targets in the setting of COVID-19 treatment in critically ill patients vol.101, pp.no.pb, 2014, https://doi.org/10.1016/j.intimp.2021.108257
  79. Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells vol.140, pp.None, 2014, https://doi.org/10.1016/j.mvr.2021.104305