Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Sphingosylphosphorylcholine Induces Thrombospondin-1 Secretion in MCF10A Cells via ERK2

  • Received : 2016.10.11
  • Accepted : 2017.01.09
  • Published : 2017.11.01
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Abstract

Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and $Ca^{2+}$ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia. TSP-1 promotes aggressive phenotype via epithelial mesenchymal transition (EMT). The relationship between SPC and TSP-1 is unclear. We found SPC induced EMT leading to mesenchymal morphology, decrease of E-cadherin expression and increases of N-cadherin and vimentin. SPC induced secretion of thrombospondin-1 (TSP-1) during SPC-induced EMT of various breast cancer cells. Gene silencing of TSP-1 suppressed SPC-induced EMT as well as migration and invasion of MCF10A cells. An extracellular signal-regulated kinase inhibitor, PD98059, significantly suppressed the secretion of TSP-1, expressions of N-cadherin and vimentin, and decrease of E-cadherin in MCF10A cells. ERK2 siRNA suppressed TSP-1 secretion and EMT. From online PROGgene V2, relapse free survival is low in patients having high TSP-1 expressed breast cancer. Taken together, we found that SPC induced EMT and TSP-1 secretion via ERK2 signaling pathway. These results suggests that SPC-induced TSP-1 might be a new target for suppression of metastasis of breast cancer cells.

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References

  1. Adams, J. C. and Tucker, R. P. (2000) The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Dev. Dyn. 218, 280-299. https://doi.org/10.1002/(SICI)1097-0177(200006)218:2<280::AID-DVDY4>3.0.CO;2-0
  2. Beil, M., Micoulet, A., von Wichert, G., Paschke, S., Walther, P., Omary, M. B., Van Veldhoven, P. P., Gern, U., Wolff-Hieber, E., Eggermann, J.,Waltenberger, J., Adler, G., Spatz, J. and Seufferlein, T. (2003) Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Nat. Cell Biol. 5, 803-811. https://doi.org/10.1038/ncb1037
  3. Boguslawski, G., Lyons, D., Harvey, K. A., Kovala, A. T. and English, D. (2000) Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis. Biochem. Biophys. Res. Commun. 272, 603-609. https://doi.org/10.1006/bbrc.2000.2822
  4. Calcerrada, M. C., Miguel, B. G., Catalan, R. E. and Martinez, A. M. (1999) Sphingosylphosphorylcholine increases calcium concentration in isolated brain nuclei. Neurosci. Res. 33, 229-232. https://doi.org/10.1016/S0168-0102(99)00004-8
  5. Campone, M., Valo, I., Jezequel, P., Moreau, M., Boissard, A., Campion, L., Loussouarn, D., Verriele, V., Coqueret, O. and Guette, C. (2015) Prediction of recurrence and survival for triple-negative breast cancer (TNBC) by a protein signature in tissue samples. Mol. Cell Proteomics 14, 2936-2946. https://doi.org/10.1074/mcp.M115.048967
  6. Cao, Z., Shang, B., Zhang, G., Miele, L., Sarkar, F. H., Wang, Z. and Zhou, Q. (2013) Tumor cell-mediated neovascularization and lymphangiogenesis contrive tumor progression and cancer metastasis. Biochim. Biophys. Acta 1836, 273-286.
  7. De, U., Kundu, S., Patra, N., Ahn, M. Y., Ahn, J. H., Son, J. Y., Yoon, J. H., Moon, H. R., Lee, B. M. and Kim, H. S. (2015) A new histone deacetylase inhibitor, MHY219, inhibits the migration of human prostate cancer cells via HDAC1. Biomol. Ther. (Seoul) 23, 434-441. https://doi.org/10.4062/biomolther.2015.026
  8. Eccles, S. A. and Welch, D. R. (2007) Metastasis: recent discoveries and novel treatment strategies. Lancet 369, 1742-1757. https://doi.org/10.1016/S0140-6736(07)60781-8
  9. Farhan, H. and Rabouille, C. (2011) Signalling to and from the secretory pathway. J. Cell Sci. 124, 171-180. https://doi.org/10.1242/jcs.076455
  10. Firlej, V., Mathieu, J. R., Gilbert, C., Lemonnier, L., Nakhle, J., Gallou-Kabani, C., Guarmit, B., Morin, A., Prevarskaya, N., Delongchamps, N. B. and Cabon, F. (2011) Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res. 71, 7649-7658. https://doi.org/10.1158/0008-5472.CAN-11-0833
  11. Fosu-Mensah, N., Peris, M.S., Weeks, H.P., Cai, J. and Westwell, A.D. (2015) Advances in small-molecule drug discovery for triple-negative breast cancer. Future Med. Chem. 7, 2019-2039. https://doi.org/10.4155/fmc.15.129
  12. Foulkes, W. D., Smith, W. D. and Reis-Filho, J. S. (2010) Triple-negative breast cancer. N. Engl. J. Med. 363, 1938-1948. https://doi.org/10.1056/NEJMra1001389
  13. Ghajar, C. M., Peinado, H., Mori, H., Matei, I. R., Evason, K. J., Brazier, H., Almeida, D., Koller, A., Hajjar, K. A., Stainier, D. Y., Chen, E. I., Lyden, D. and Bissell, M. J. (2013) The perivascular niche regulates breast tumour dormancy. Nat. Cell Biol. 15, 807-817. https://doi.org/10.1038/ncb2767
  14. Goswami, C. P. and Nakshatri, H. (2014) PROGgeneV2: enhancements on the existing database. BMC Cancer 14, 970. https://doi.org/10.1186/1471-2407-14-970
  15. Horiguchi, H., Yamagata, S., Rong Qian, Z., Kagawa, S. and Sakashita, N. (2013) Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis. J. Med. Invest. 60, 91-96. https://doi.org/10.2152/jmi.60.91
  16. Ignatov, A., Lintzel, J., Hermans-Borgmeyer, I., Kreienkamp, H. J., Joost P., Thomsen, S., Methner, A. and Schaller, H. C. (2003) Role of the G-protein-coupled receptor GPR12 as highaffinityreceptor for sphingosylphosphorylcholine and its expression and functionin brain development. J. Neurosci. 23, 907-914. https://doi.org/10.1523/JNEUROSCI.23-03-00907.2003
  17. Im, D. S. (2003) Linking Chinese medicine and G-protein-coupled receptors. Trends Pharmacol. Sci. 24, 2-4. https://doi.org/10.1016/S0165-6147(02)00012-3
  18. Jayachandran, A., Anaka, M., Prithviraj, P., Hudson, C., McKeown, S. J., Lo, P. H., Vella, L. J., Goding, C. R., Cebon, J. and Behren, A. (2014) Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma. Oncotarget 5, 5782-5797.
  19. Jeon, E. S., Moon, H. J., Lee, M. J., Song, H. Y., Kim, Y. M., Bae, Y. C., Jung, J. S. and Kim, J. H. (2006) Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism. J. Cell Sci. 119, 4994-5005. https://doi.org/10.1242/jcs.03281
  20. Jeong, Y. H., Park, J. S., Kim, D. H. and Kim, H.-S. (2016) Lonchocarpine increases Nrf2/ARE-mediated antioxidant enzyme expression by modulating AMPK and MAPK signaling in brain astrocytes. Biomol. Ther. (Seoul) 24, 581-588. https://doi.org/10.4062/biomolther.2016.141
  21. Jimenez, B., Volpert, O. V., Crawford, S. E., Febbraio, M., Silverstein, R. L. and Bouck, N. (2000) Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat. Med. 6, 41-48. https://doi.org/10.1038/71517
  22. Kalluri, R. and Weinberg, R. A. (2009) The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420-1428. https://doi.org/10.1172/JCI39104
  23. Kim, E. J., Kim, H. J., Park, M. K., Kang, G. J., Byun, H. J., Lee, H. and Lee, C. H. (2015) Cardamonin suppresses TGF-${\beta}1$-induced epithelial mesenchymal transition via restoring protein phosphatase 2A expression. Biomol. Ther. (Seoul) 23, 141-148. https://doi.org/10.4062/biomolther.2014.117
  24. Kim, H. J., Choi, W. J. and Lee, C. H. (2015) Phosphorylation and reorganization of keratin networks: Implications for carcinogenesis and epithelial mesenchymal transition. Biomol. Ther. (Seoul) 23, 301-312. https://doi.org/10.4062/biomolther.2015.032
  25. Kim, H. J., Kang, G. J., Kim, E. J., Park, M. K., Byun, H. J., Nam, S., Lee, H. and Lee, C. H. (2016) Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation. Biochim. Biophys. Acta 1862, 1533-1543. https://doi.org/10.1016/j.bbadis.2016.05.010
  26. Kurokawa, T., Yumiya, Y., Fujisawa, H., Shirao, S., Kashiwagi, S., Sato, M., Kishi, H., Miwa, S., Mogami, K., Kato, S., Akimura, T., Soma, M., Ogasawara, K., Ogawa, A., Kobayashi, S. and Suzuki, M. (2009) Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid after subarachnoid hemorrhage: a possible role as a spasmogen. J. Clin. Neurosci. 16, 1064-1068. https://doi.org/10.1016/j.jocn.2009.01.010
  27. Lawler, J. W., Slayter, H. S. and Coligan, J. E. (1978) Isolation and characterization of a high molecular weight glycoprotein from human blood platelets. J. Biol. Chem. 253, 8609-8616.
  28. Lee, H. Y., Lee, S. Y., Kim, S. D., Shim, J. W., Kim, H. J., Jung, Y. S., Kwon, J. Y., Baek, S. H., Chung, J. and Bae, Y. S. (2011) Sphingosylphosphorylcholine stimulates CCL2 production from human umbilical vein endothelial cells. J. Immunol. 186, 4347-4353. https://doi.org/10.4049/jimmunol.1002068
  29. Lim, S. C., Lee, K. M. and Kang, T. J. (2015) Chitin from cuttlebone activates inflammatory cells to enhance the cell migration. Biomol. Ther. (Seoul) 23, 333-338. https://doi.org/10.4062/biomolther.2015.062
  30. Meyer zu Heringdorf, D., Himmel, H. M. and Jakobs, K. H. (2002) Sphingosylphosphorylcholine-biological functions and mechanisms of action. Biochim. Biophys. Acta 1582, 178-189. https://doi.org/10.1016/S1388-1981(02)00154-3
  31. Murphy-Ullrich, J. E. and Poczatek, M. (2000) Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev. 11, 59-69. https://doi.org/10.1016/S1359-6101(99)00029-5
  32. Nieto, M. A., Huang, R. Y., Jackson, R. A. and Thiery, J. P. (2016) EMT: 2016. Cell 166, 21-45. https://doi.org/10.1016/j.cell.2016.06.028
  33. Nixon, G. F., Mathieson, F. A. and Hunter, I. (2008) The multi-functional role of sphingosylphosphorylcholine. Prog. Lipid Res. 47, 62-75. https://doi.org/10.1016/j.plipres.2007.11.001
  34. Park, K. S., Kim, H. K, Lee, J. H., Choi, Y. B., Park, S. Y., Yang, S. H., Kim, S. Y. and Hong, K. M. (2010) Transglutaminase 2 as a cisplatin resistance marker in non-small cell lung cancer. J. Cancer Res. Clin. Oncol. 136, 493-502. https://doi.org/10.1007/s00432-009-0681-6
  35. Park, M. K., You, H. J., Lee, H. J., Kang, J. H., Oh, S. H., Kim, S. Y. and Lee, C. H. (2013) Transglutaminase-2 induces N-cadherin expression in TGF-beta1-induced epithelial mesenchymal transition via c-Jun-N-terminal kinase activation by protein phosphatase 2A down-regulation. Eur. J. Cancer 49, 1692-1705. https://doi.org/10.1016/j.ejca.2012.11.036
  36. Park, M. K., Park, S., Kim, H. J., Kim, E. J., Kim, S. Y., Kang, G. J., Byun, H. J., Kim, S. H., Lee, H. and Lee, C. H. (2016) Novel effects of FTY720 on perinuclear reorganization of keratinnetwork induced by sphingosylphosphorylcholine: Involvement of protein phosphatase 2A and G-protein-coupled receptor-12. Eur. J. Pharmacol. 775, 86-95. https://doi.org/10.1016/j.ejphar.2016.02.024
  37. Retraction (2005) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J. Biol. Chem. 280, 43280.
  38. Retraction (2006) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat. Cell Biol. 8, 299.
  39. Schlyer, S. and Horuk, R. (2006) I want a new drug: G-protein-coupled receptors in drug development. Drug Discov. Today 11, 481-493. https://doi.org/10.1016/j.drudis.2006.04.008
  40. Schultz-Cherry, S., Lawler, J. and Murphy-Ullrich, J. E. (1994) The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-${\beta}$. J. Biol. Chem. 269, 26783-26788.
  41. Seufferlein, T. and Rozengurt, E. (1995) Sphingosylphosphorylcholine rapidly induces tyrosine phosphorylation of p125FAK and paxillin, rearrangement of the actin cytoskeleton and focal contact assembly. Requirement of p21rho in the signaling pathway. J. Biol. Chem. 270, 24343-24351. https://doi.org/10.1074/jbc.270.41.24343
  42. Shin, S. and Blenis, J. (2010) ERK2/Fra1/ZEB pathway induces epithelial-to-mesenchymal transition. Cell Cycle 9, 2483-2484. https://doi.org/10.4161/cc.9.13.12270
  43. Shin, S., Dimitri, C. A., Yoon, S. O., Dowdle, W. and Blenis, J. (2010) ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events. Mol. Cell 38, 114-127. https://doi.org/10.1016/j.molcel.2010.02.020
  44. Sid, B., Langlois, B., Sartelet, H., Bellon, G., Dedieu, S. and Martiny, L. (2008) Thrombospondin-1 enhances human thyroid carcinoma cell invasion through urokinase activity. Int. J. Biochem. Cell Biol. 40, 1890-1900. https://doi.org/10.1016/j.biocel.2008.01.023
  45. Sorensen, K. P., Thomassen, M., Tan, Q., Bak, M., Cold, S., Burton, M., Larsen, M. J. and Kruse, T. A. (2013) Long non-coding RNA HOTAIR is an independent prognostic marker of metastasis in estrogen receptor-positive primary breast cancer. Breast Cancer Res. Treat. 142, 529-536. https://doi.org/10.1007/s10549-013-2776-7
  46. Tiwari, N., Gheldof, A., Tatari, M. and Christofori, G. (2012) EMT as the ultimate survival mechanism of cancer cells. Semin. Cancer Biol. 22, 194-207. https://doi.org/10.1016/j.semcancer.2012.02.013
  47. Valastyan, S. and Weinberg, R. A. (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147, 275-292. https://doi.org/10.1016/j.cell.2011.09.024
  48. Wang, X., Zhu, Y., Ma, Y., Wang, J., Zhang, F., Xia, Q. and Fu, D. (2013) The role of cancer stem cells in cancer metastasis: new perspective and progress. Cancer Epidemiol. 37, 60-63. https://doi.org/10.1016/j.canep.2012.07.007
  49. Wang, Y., Klijn, J. G., Zhang, Y., Sieuwerts, A. M, Look, M. P., Yang, F., Talantov, D., Timmermans, M., Meijer-van Gelder, M. E., Yu, J., Jatkoe, T., Berns, E. M., Atkins, D. and Foekens, J. A. (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 365, 671-679. https://doi.org/10.1016/S0140-6736(05)70933-8
  50. Xiao, Y. J., Schwartz, B., Washington, M., Kennedy, A., Webster, K., Belinson, J. and Xu, Y. (2001) Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs nonmalignant ascitic fluids. Anal. Biochem. 290, 302-313. https://doi.org/10.1006/abio.2001.5000
  51. Xu, Y. (2002) Sphingosylphosphorylcholine and lysophosphatidylcholine: G protein-coupled receptors and receptor-mediated signal transduction. Biochim. Biophys. Acta 1582, 81-88. https://doi.org/10.1016/S1388-1981(02)00140-3
  52. Xu, Y., Zhu, K., Hong, G., Wu, W., Baudhuin, L. M., Xiao, Y. and Damron, D. S., (2000) Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat. Cell Biol. 2, 261-267. https://doi.org/10.1038/35010529
  53. Yang, C. R., Wei, Y., Qi, S. T., Chen L., Zhang, Q. H., Ma J. Y., Luo Y. B., Wang Y. P., Hou, Y., Schatten, H., Liu, Z. H. and Sun, Q. Y. (2012) The G protein coupled receptor 3 is involved in cAMP and cGMP signaling and maintenance of meiotic arrest in porcine oocytes, PLoS ONE 7, e38807. https://doi.org/10.1371/journal.pone.0038807
  54. Yee, K. O., Connolly, C. M., Duquette, M., Kazerounian, S., Washington, R. and Lawler, J. (2009) The effect of thrombospondin-1 on breast cancer metastasis. Breast Cancer Res. Treat. 114, 85-96. https://doi.org/10.1007/s10549-008-9992-6
  55. Zheng, M., Zhang, X., Min, C., Choi, B. G., Oh, I. J. and Kim, K. M. (2016) Functional regulation of dopamine D3 receptor through interaction with PICK1. Biomol. Ther. (Seoul) 24, 475-481. https://doi.org/10.4062/biomolther.2016.015
  56. Zhu, K., Baudhuin, L. M., Hong, G., Williams, F. S., Cristina, K. L., Kabarowski, J. H., Witte, O. N. and Xu, Y. (2001) Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J. Biol. Chem. 276, 41325-41335. https://doi.org/10.1074/jbc.M008057200

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