Identification of arachidonic acid pathways required for the invasive and metastatic activity of malignant tumor cells

Reuven Reich*, George R. Martin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

Metastasis is a complex process, almost a cascade, involving multiple steps and activities. However, an important factor is that malignant cells are able to penetrate through the multiple basement membrane barriers surrounding tissues, blood vessels, nerves and muscle that would otherwise block their dissemination. Penetration of malignant tumor cells through basement membrane is an active process requiring proteolysis. We report here that inhibitors of both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism convert mouse melanoma and human fibrosarcoma cells to a non invasive state by reducing the production of MMP-2, an enzyme required for the degradation of basement membranes. Specific metabolites of each pathway, i.e. PGF(2α) and 5-HPETE, are able to transcend the block and restore collagenase production, invasiveness in vitro and metastatic activity in vivo. These studies indicate a key role for arachidonic acid metabolites in metastasis and suggest novel therapeutic approaches for inhibiting the spread of cancer.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalProstaglandins
Volume51
Issue number1
DOIs
StatePublished - 1996

Keywords

  • arachidonic acid
  • collagenase
  • cyclooxygenase
  • invasion
  • lipoxygenase
  • metastasis

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