Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential

Masahiko Tsujii, Sunao Kawano, Raymond N. Dubois

    Research output: Contribution to journalArticlepeer-review

    1302 Scopus citations

    Abstract

    Recent epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in individuals who take nonsteroidal antiinflammatory drugs on a regular basis compared with those not taking these agents. One property shared by all of these drugs is their ability to inhibit cyclooxygenase (COX), a key enzyme in the conversion of arachidonic acid tn prostaglandins. Two isoforms of cox have been characterized, COX-1 and COX- 2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. Human colon cancer cells (Caco-2) were permanently transfected with a COX-2 expression vector or the identical vector lacking the COX-2 insert. The Caco-2 cells, which constitutively expressed COX-2, acquired increased invasiveness compared with the parental Caco-2 cells or the vector transfected control cells. Biochemical changes associated with this phenotypic change included activation of metalloproteinase-2 and increased rna levels for the membrane-type metalloproteinase. Increased invasiveness and prostaglandin production were reversed by treatment with sulindac sulfide, a known COX inhibitor. These studies demonstrate that constitutive expression of COX-2 can lead to phenotypic changes that alter the metastatic potential of colorectal cancer cells.

    Original languageEnglish (US)
    Pages (from-to)3336-3340
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume94
    Issue number7
    DOIs
    StatePublished - Apr 1 1997

    Keywords

    • invasion
    • metalloproteinase
    • prostaglandins
    • sulindac sulfide)

    ASJC Scopus subject areas

    • General

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