Host cyclooxygenase-2 modulates carcinoma growth

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

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    634 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

    ASJC Scopus subject areas

    • Medicine(all)

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    Williams, C. S., Tsujii, M., Reese, J., Dey, S. K., & DuBois, R. N. (2000). Host cyclooxygenase-2 modulates carcinoma growth. Journal of Clinical Investigation, 105(11), 1589-1594. https://doi.org/10.1172/JCI9621