Host cyclooxygenase-2 modulates carcinoma growth.

Williams CS, Tsujii M, Reese J, Dey SK, DuBois RN
J Clin Invest. 2000 105 (11): 1589-94

PMID: 10841517 · PMCID: PMC300858 · DOI:10.1172/JCI9621

Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in carcinogenesis remains unclear. We evaluated the contribution of host-derived COX-1 and COX-2 in tumor growth using both genetic and pharmacological approaches. Lewis lung carcinoma (LLC) cells grow rapidly as solid tumors when implanted in C57BL/6 mice. We found that tumor growth was markedly attenuated in COX-2(-/-), but not COX-1(-/-) or wild-type mice. Treatment of wild-type C57BL/6 mice bearing LLC tumors with a selective COX-2 inhibitor also reduced tumor growth. A decrease in vascular density was observed in tumors grown in COX-2(-/-) mice when compared with those in wild-type mice. Because COX-2 is expressed in stromal fibroblasts of human and rodent colorectal carcinomas, we evaluated COX-2(-/-) mouse fibroblasts and found a 94% reduction in their ability to produce the proangiogenic factor, VEGF. Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%.

MeSH Terms (18)

Animals Blotting, Western Carcinoma, Lewis Lung Cyclooxygenase 1 Cyclooxygenase 2 Endothelial Growth Factors Isoenzymes Lymphokines Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Neoplasms, Experimental Neovascularization, Pathologic Prostaglandin-Endoperoxide Synthases Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors

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