Exp Mol Med.  2007 Aug;39(4):469-476.

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

• Lee EJ
• Choi EM
• Kim SR
• Park JH
• Kim H
• Ha KS
• Kim YM
• Kim SS
• Choe M
• Kim JI
• Han JA

Abstract

Osteosarcoma is the most common primary bone tumor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be closely associated with tumor growth and metastasis in several 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 E(2) 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, migration and invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.

Keyword

cell movement; cell proliferation; cyclooxygenase-2; matrix metalloproteinases; osteosarcoma

MeSH Terms

Bone Neoplasms/*enzymology/pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclooxygenase 2/biosynthesis/*physiology
Cyclooxygenase 2 Inhibitors/pharmacology
Dinoprostone/pharmacology
Enzyme Activation
Humans
Matrix Metalloproteinase 2/metabolism
Matrix Metalloproteinase 9/metabolism
Neoplasm Invasiveness
Nitrobenzenes/pharmacology
Osteosarcoma/*enzymology/pathology
Pyrazoles/pharmacology
Sulfonamides/pharmacology