CYCLOOXYGENASE REGULATES ANGIOGENESIS INDUCED BY COLON-CANCER CELLS

To explore the role of cyclooxygenase (COX) in endothelial cell migrat ion and angiogenesis, we have used two in vitro model systems involvin g coculture of endothelial cells with colon carcinoma cells. COX-2-ove rexpressing cells produce prostaglandins, proangiogenic factors, and s timulate both endothelial migration and tube formation, while control cells have little activity. The effect is inhibited by antibodies to c ombinations of angiogenic factors, by NS-398 (a selective COX-2 inhibi tor), and by aspirin. NS-398 does not inhibit production of angiogenic factors or angiogenesis induced by COX-2-negative cells. Treatment of endothelial cells with aspirin or a COX-1 antisense oligonucleotide i nhibits COX-1 activity/expression and suppresses tube formation. Cyclo oxygenase regulates colon carcinoma-induced angiogenesis by two mechan isms: COX-2 can modulate production of angiogenic factors by colon can cer cells, while COX-1 regulates angiogenesis in endothelial cells.