TY - JOUR
T1 - Host cyclooxygenase-2 modulates carcinoma growth
AU - Williams, Christopher S.
AU - Tsujii, Masahiko
AU - Reese, Jeff
AU - Dey, Sudhansu K.
AU - DuBois, Raymond N.
PY - 2000/6
Y1 - 2000/6
N2 - Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for rolorectal 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 rolorectal 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%.
AB - Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for rolorectal 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 rolorectal 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%.
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U2 - 10.1172/JCI9621
DO - 10.1172/JCI9621
M3 - Article
C2 - 10841517
AN - SCOPUS:0034089566
SN - 0021-9738
VL - 105
SP - 1589
EP - 1594
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -