[HTML][HTML] Host cyclooxygenase-2 modulates carcinoma growth

CS Williams, M Tsujii, J Reese, SK Dey… - The Journal of …, 2000 - Am Soc Clin Investig
The Journal of clinical investigation, 2000Am Soc Clin Investig
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 …
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%.
The Journal of Clinical Investigation