Host cyclooxygenase-2 modulates carcinoma growth

Christopher S. Williams, Masahiko Tsujii, Jeff Reese, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticlepeer-review

641 Scopus citations

Abstract

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%.

Original languageEnglish (US)
Pages (from-to)1589-1594
Number of pages6
JournalJournal of Clinical Investigation
Volume105
Issue number11
DOIs
StatePublished - Jun 2000
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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