Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지

Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells

Lee, Eun-Jeong;Choi, Eun-Mi;Kim, So-Ra;Park, Jung-Hea;Kim, Hyun-Sook;Ha, Kwon-Soo;Kim, Young-Myeong;Kim, Sung-Soo;Choe, Myeon;Kim, Jong-Il;Han, Jeong-A

  • Published : 20070800
⟨ Previous Next ⟩

Abstract

Osteosarcoma is the most comon primary bone tu-mor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be close-ly associated with tumor growth and metastasis in sev-eral kinds of human tumors, the function of COX-2 in osteosarcoma is unclear. Therefore, to investigate the function of COX-2 in osteosarcoma, we established stable cell lines overexpressing COX-2 in U2OS human osteosarcoma cells. COX-2 overexpression as well as prostaglandin E2 treatment promoted proliferation of U2OS cells. In addition, COX-2 overexpression enhanced mobility and invasiveness of U2OS cells, which was accompanied by increases of matrix metalloproteinase- 2 and -9 (MMP-2 and -9) activities. Selective COX-2 inhibitors, NS-398 and celecoxib, inhibited cell proliferation and abrogated the enhanced mobility, invasiveness and MMP activities induced by COX-2 overexpression. These results suggest that COX-2 is directly associated with cell proliferation, migrationand invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.

Keywords

References

  1. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a $G_s-axin-{\beta}-catenin$ signaling axis. Sience 2005;310:1504-10 https://doi.org/10.1126/science.1116221
  2. Chen Q, Shinohara N, Abe T, Watanabe T, Nonomura K, Koyanagi T. Significance of COX-2 expression in human renal cell carcinoma cell lines. Int J Cancer 2004;108:825-32 https://doi.org/10.1002/ijc.11646
  3. Davies KJ. The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life 1999;48:41-7 https://doi.org/10.1080/713803463
  4. Dickens DS, Kozielski R, Khan J, Forus A, Cripe TP. Cyclooxygenase-2 expression in pediatric sarcomas. Pediatr Dev Pathol 2002;5:356-64 https://doi.org/10.1007/s10024-002-0005-1
  5. Dickens DS, Kozielski R, Leavey PJ, Timmons C, Cripe TP, Cyclooxygenase-2 expression does not correlate with outcome in osteosarcoma or rhabdomyosarcoma. J Pediatr Hematol Oncol 2003;25:282-5 https://doi.org/10.1097/00043426-200304000-00003
  6. Fujita H, Koshida K, Keller ET, Takahashi Y, Yoshimito T, Namiki M, Mizokami A. Cyclooxygenase-2 promotes prostate cancer progression. Prostate 2002;53:232-40 https://doi.org/10.1002/pros.10152
  7. Han C, Wu T. Cyclooxygenase-2-derived prostaglandin $E_2$ promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. J Biol Chem 2005;280:24053-63 https://doi.org/10.1074/jbc.M500562200
  8. Klein G, Vellenga E, Fraaije MW, Kamps WA, de Bont ESJM. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 2004;50:87-100 https://doi.org/10.1016/j.critrevonc.2003.09.001
  9. Klein RD, Pelt CSV, Sabichi AL, Cerda JD, Fischer SM, Furstenberger G, Muller-Decker K. Transitional cell hyperplasia and carcinomas in urinary bladders of transgenic mice with keratin 5 promoter-driven cyclooxygenase-2 overexpression. Cancer Res 2005;65:1808-13 https://doi.org/10.1158/0008-5472.CAN-04-3567
  10. Krysan K, Reckamp KL, Dalwadi H, Sharma S, Rozengurt E, Dohadqala M, Dubinett SM. Prostaglandin $E_2$ activates mitogen-activated protein kinase/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an epidermal growth factor receptor-independent manner. Cancer Res 2005;65:6275-81 https://doi.org/10.1158/0008-5472.CAN-05-0216
  11. Larkins TL, Nowell M, Singh S, Sanford GL. Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer 2006;181:1-12
  12. Li G, Yang T, Yan J. Cyclooxygenase-2 increased the angiogenic and metastatic potential of tumor cells. Biochem Biophys Res Commun 2002;299:886-90 https://doi.org/10.1016/S0006-291X(02)02707-9
  13. Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF, Hla T. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 2001;276:18563-9 https://doi.org/10.1074/jbc.M010787200
  14. Longhi A, Errani C, de Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat Rev 2006;32:423-36 https://doi.org/10.1016/j.ctrv.2006.05.005
  15. Naruse T, Nishida Y, Hosono K, Ishiguro N. Meloxicam inhibits osteosarcoma growth, invasiveness and metastasis by COX-2-dependent and independent routes. Carcinogenesis 2006;27:584-92 https://doi.org/10.1093/carcin/bgi240
  16. Sanbino MA, Ghilardi JR, Jongen JL, Keyser CP, Luger NM, Mach DB, Peters CB, Rogers SD, Schwei MJ, de Felipe C, Mantyh PW. Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res 2002;62:7343-9
  17. Sheng H, Shao J, Washington MK, DuBois RN. Prostagladin $E_2$ increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001;276:18075-81 https://doi.org/10.1074/jbc.M009689200
  18. Singh B, Berry JA, Shoher A, Ramakrishnan V, Lucci A. COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol 2005;26:1393-9
  19. Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996;271:33157-60 https://doi.org/10.1074/jbc.271.52.33157
  20. Tsujii M, Kawano S, DuBois RN, Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 1997;94:3336-40
  21. Xu Z, Choudhary S, Voznesensky O, Mehrotra M, Woodard M, Hansen M, Herschman H, Pilbeam C. Overexpression of COX-2 in human osteosarcoma cells decreases proliferation and increases apoptosis. Cancer Res 2006;66:6657-64 https://doi.org/10.1158/0008-5472.CAN-05-3624
  22. Yoon SO, Yun CH, Chung AS. Dose effect of oxidative stress on signal transduction on aging. Mech Ageing Dev 2002; 123:1597-604 https://doi.org/10.1016/S0047-6374(02)00095-7