Cyclooxygenase regulates angiogenesis induced by colon cancer cells

Masahiko Tsujii, Sunao Kawano, Shingo Tsuji, Hitoshi Sawaoka, Masatsugu Hori, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    2147 Scopus citations

    Abstract

    To explore the role of cyclooxygenase (COX) in endothelial cell migration and angiogenesis, we have used two in vitro model systems involving coculture of endothelial cells with colon carcinoma cells. COX-2- overexpressing cells produce prostaglandins, proangiogenic factors, and stimulate both endothelial migration and tube formation, while control cells have little activity. The effect is inhibited by antibodies to combinations of angiogenic factors, by NS-398 (a selective COX-2 inhibitor), and by aspirin. NS-398 does not inhibit production of angiogenic factors or angiogenesis induced by COX-2-negative cells. Treatment of endothelial cells with aspirin or a COX-1 antisense oligonucleotide inhibits COX-1 activity/expression and suppresses tube formation. Cyclooxygenase regulates colon carcinoma-induced angiogenesis by two mechanisms: COX-2 can modulate production of angiogenic factors by colon cancer cells, while COX-1 regulates angiogenesis in endothelial cells.

    Original languageEnglish (US)
    Pages (from-to)705-716
    Number of pages12
    JournalCell
    Volume93
    Issue number5
    DOIs
    StatePublished - May 29 1998

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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