Nitric oxide, prostanoids, cyclooxygenase, and angiogenesis in colon and breast cancer.
OBJECTIVE
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 inducible form of nitric oxide synthase (iNOS), PGI(2), and TXA(2) in cancerous and adjoining areas of specimens from human colon and breast cancer obtained during surgery. Additionally, we investigated differences in expression and histological localization of COX-2 in colon and breast cancer.


METHODS
Specimens were obtained during surgery, one centrally located, the second from an adjacent, cancer-free area. Activity of iNOS was determined, using the conversion of L-[(14)C]arginine to L-[(14)C]citrulline. PGI(2) and TXA(2) were measured as their stable metabolites, using enzyme immunoassay. A standard immunoperoxidase method was used for immunohistochemical expression of COX-2.


RESULTS
Significant differences in iNOS, PGI(2), and TXA(2) expressions between colon and breast cancer were noted, with an enhanced expression of COX-2 in colon cancer, including the cancerous, adjoining, and stromatous fields.


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 potential for neoplastic cells in this area. Inflammatory changes in the tissue adjoining the cancer may play a role. COX-2 may result in the formation of new blood vessels and the spread of cancer.
Bing
R J
RJ
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, CA 91101, USA. cardio@hmri.org
Miyataka
M
M
Rich
K A
KA
Hanson
N
N
Wang
X
X
Slosser
H D
HD
Shi
S R
SR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases