Nitric oxide, prostanoids, cyclooxygenase, and angiogenesis in colon and breast cancer

Purpose: Several studies have shown an overexpression of cyclooxygenase-2 ( COX-2) and elevated levels of prostacyclin (PGI(2)) and thromboxane (TXA(2) ) in colon cancer. In this report, we determined the distribution of induci ble form of nitric oxide synthase (iNOS), PGI(2), and TXA(2) in cancerous a nd adjoining areas of specimens from human colon and breast cancer obtained during surgery. Additionally, we investigated differences in expression an d histological localization of COX-2 in colon and breast cancer. Experimental Design: Specimens were obtained during surgery, one centrally located, the second from an adjacent, cancer-free area. Activity of iNOS wa s determined, using the conversion of L-[C-14]arginine to L-[C-14]citrullin e. PGI(2) and TXA(2) were measured as their stable metabolites, using enzym e immunoassay. A standard immunoperoxidase method was used for immunohistoc hemical expression of COX-2. Results: Significant differences in iNOS, PGI(2), and TXA(2) expressions be tween colon and breast cancer were noted, with an enhanced expression of CO X-2 in colon cancer, including the cancerous, adjoining, and stromatous fie lds. Conclusions: Increased expression of iNOS and production of prostanoids in colon cancer parallels the increase in COX-2, confirming the importance of this enzyme in colon cancer. The overexpression of COX-2, prostanoids, and nitric oxide in areas adjoining the tumor indicates increased metastatic po tential for neoplastic cells in this area. Inflammatory changes in the tiss ue adjoining the cancer may play a role. COX-2 may result in the formation of new blood vessels and the spread of cancer.