Asian Pacific Journal of Cancer Prevention

  • 제13권6호
  • /
  • Pages.2823-2828
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  • 2012
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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New Model of In-situ Xenograft Lymphangiogenesis by a Human Colonic Adenocarcinoma Cell Line in Nude Mice

  • Sun, Jian-Jun (Department of Surgery, Tongji Hospital, Tongji University School of Medicine) ;
  • Jing, Wei (Department of Surgery, Tongji Hospital, Tongji University School of Medicine) ;
  • Ni, Yan-Yan (Department of Surgery, Tongji Hospital, Tongji University School of Medicine) ;
  • Yuan, Xiao-Jian (Department of Surgery, Tongji Hospital, Tongji University School of Medicine) ;
  • Zhou, Hai-Hua (Department of Surgery, Tongji Hospital, Tongji University School of Medicine) ;
  • Fan, Yue-Zu (Department of Surgery, Tongji Hospital, Tongji University School of Medicine)
  • 발행 : 2012.06.30
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초록

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

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참고문헌

  1. Achen MG, Mann GB, Stacker SA (2006). Targeting lymphangiogenesis to prevent tumor metastasis. Br J Cancer, 94, 1355-60. https://doi.org/10.1038/sj.bjc.6603120
  2. Achen MG, Stacker SA (2006). Tumor lymphangiogenesis and metastatic spread - New players begin to emerge. Int J Cancer, 119, 1755-60. https://doi.org/10.1002/ijc.21899
  3. Breiteneder-Geleff S (1999). Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: Podoplanin as a specific marker for lymphatic endothelium. Am J Pathol, 154, 385-94. https://doi.org/10.1016/S0002-9440(10)65285-6
  4. Fidler IJ (1990). Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res, 50, 6130-8.
  5. Fidler IJ (2003). The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer, 3, 453-8. https://doi.org/10.1038/nrc1098
  6. Flatmark K, Maelandsmo GM, Martinsen M, et al (2004). Twelve colorectal cancer cell lines exhibit highly variable growth and metastatic capacities in an orthotopic model in nude mice. Eur J Cancer, 40, 1593-8. https://doi.org/10.1016/j.ejca.2004.02.023
  7. Jackson, DG, Prevo R, Clasper S, et al (2001). LYVE-1, the lymphatic system and tumor lymphangiogenesis. Trends Immunol, 22, 317-21. https://doi.org/10.1016/S1471-4906(01)01936-6
  8. Kowanetz M, Ferrara N (2006). Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res, 12, 5018-22. https://doi.org/10.1158/1078-0432.CCR-06-1520
  9. Kozlowski M, Naumnik W, Niklinski J, et al (2011). Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer. Folia Histochem Cytobiol, 49, 90-7. https://doi.org/10.5603/FHC.2011.0013
  10. Kubo H, Fujiwara T, Jussila L, et al (2000). Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis. Blood, 96, 546-53.
  11. Liersch R, Biermann C, Mesters RM, et al (2010). Lymphangiogenesis in cancer: current perspectives. Recent Results Cancer Res, 180, 115-35. https://doi.org/10.1007/978-3-540-78281-0_8
  12. McColl BK, Loughran SJ, Davydova N, et al (2005). Mechanisms of lymphangiogenesis: targets for blocking the metastatic spread of cancer. Curr Cancer Drug Targets, 5, 561-71. https://doi.org/10.2174/156800905774932833
  13. Mylona E, Alexandrou P, Mpakali A, et al (2007). Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol, 33, 294-300 https://doi.org/10.1016/j.ejso.2006.10.015
  14. Nagahashi M, Ramachandran S, Rashid OM, et al (2010). Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol, 16, 4003-12. https://doi.org/10.3748/wjg.v16.i32.4003
  15. Prevo R, Banerji S, Ferguson DJ, et al (2001). Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. J Biol Chem, 276, 19420-30 https://doi.org/10.1074/jbc.M011004200
  16. Renyi-Vamos F, Tovari J, Fillinger J, et al (2005). Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res, 11, 7344-53. https://doi.org/10.1158/1078-0432.CCR-05-1077
  17. Sasaki H, Miura K, Horii A, et al (2008). Orthotopic implantation mouse model and cDNA microarray analysis indicates several genes potentially involved in lymph node metastasis of colorectal cancer. Cancer Sci, 99, 711-9. https://doi.org/10.1111/j.1349-7006.2008.00725.x
  18. Sundar SS, Ganesan TS (2007). Role of lymphangiogenesis in cancer. J Clin Oncol, 25, 4298-307. https://doi.org/10.1200/JCO.2006.07.1092
  19. Tsutsumi S, Kuwano H, Morinaga N, et al (2001). Animal model of para-aortic lymph node metastasis. Cancer Lett, 169, 77-85. https://doi.org/10.1016/S0304-3835(00)00622-4
  20. Wissmann C, Detmar M (2006). Pathways targeting tumor lymphangiogenesis. Clin Cancer Res, 12, 6865-8. https://doi.org/10.1158/1078-0432.CCR-06-1800
  21. Zwaans BM, Bielenberg DR (2007). Potential therapeutic strategies for lymphatic metastasis. Microvasc Res, 74, 145-58. https://doi.org/10.1016/j.mvr.2007.08.006

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  3. Establishment of human metastatic colorectal cancer model in rabbit liver: A pilot study vol.12, pp.5, 2017, https://doi.org/10.1371/journal.pone.0177212
  4. Update December 2012 vol.10, pp.4, 2012, https://doi.org/10.1089/lrb.2012.1042