Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells.
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 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, migration and invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.
Lee
Eun Jeong
EJ
Department of Biochemistry and Molecular Biology, Kangwon National University College of Medicine, Chuncheon 200-701, Korea.
Choi
Eun Mi
EM
Kim
So Ra
SR
Park
Jung Hea
JH
Kim
Hyunsook
H
Ha
Kwon Soo
KS
Kim
Young Myeong
YM
Kim
Sung Soo
SS
Choe
Myeon
M
Kim
Jong-Il
JI
Han
Jeong A
JA
D001859:Bone Neoplasms / Q000201:enzymology* / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009578:Nitrobenzenes / Q000494:pharmacology; D012516:Osteosarcoma / Q000201:enzymology* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000068579:Celecoxib; D015232:Dinoprostone