Cancer and Metastasis Reviews

, Volume 13, Issue 3–4, pp 365–396 | Cite as

12-Lipoxygenases and 12(S)-HETE: role in cancer metastasis

  • Kenneth V. Honn
  • Dean G. Tang
  • Xiang Gao
  • Igor A. Butovich
  • Bin Liu
  • Jozsef Timar
  • Wolfgang Hagmann
Article

Abstract

Arachidonic acid metabolites have been implicated in multiple steps of carcinogenesis. Their role in tumor cell metastasis, the ultimate challenge for the treatment of cancer patients, are however not well-documented. Arachidonic acid is primarily metabolized through three pathways, i.e., cyclooxygenase, lipoxygenase, and P450-dependent monooxygenase. In this review we focus our attention on one specific lipoxygenase, i.e., 12-lipoxygenase, and its potential role in modulating the metastatic process. In mammalian cells there exist three types of 12-lipoxygenases which differ in tissue distribution, preferential substrates, and profile of their metabolites. Most of these 12-lipoxygenases have been cloned and sequenced, and the molecular and biochemical determinants responsible for catalysis of specific substrates characterized. Solid tumor cells express 12-lipoxygenase mRNA, possess 12-lipoxygenase protein, and biosynthesize 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid], as revealed by numerous experimental approaches. The ability of tumor cells to generate 12(S)-HETE is positively correlated to their metastatic potential. A large collection of experimental data suggest that 12(S)-HETE is a crucial intracellular signaling molecule that activates protein kinase C and mediates the biological functions of many growth factors and cytokines such as bFGF, PDGF, EGF, and AMF. 12(S)-HETE plays a pivotal role in multiple steps of the metastatic ‘cascade’ encompassing tumor cell-vasculature interactions, tumor cell motility, proteolysis, invasion, and angiogenesis. The fact that 12-lipoxygenase is expressed in a wide diversity of tumor cell lines and 12(S)-HETE is a key modulatory molecule in metastasis provides the rationale for targeting these molecules in anti-cancer and anti-metastasis therapeutic protocols.

Key words

eicosanoids 12-lipoxygenase metastasis adhesion 12(S)-HETE protein kinase C 

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Kenneth V. Honn
    • 1
    • 2
    • 3
    • 4
  • Dean G. Tang
    • 1
  • Xiang Gao
    • 1
  • Igor A. Butovich
    • 1
    • 5
  • Bin Liu
    • 1
    • 6
  • Jozsef Timar
    • 1
    • 7
  • Wolfgang Hagmann
    • 1
    • 8
  1. 1.Divion of Cancer Biology, Department of Radiation OncologyWayne State UniversityDetroitUSA
  2. 2.Departments of ChemistryWayne State UniversityDetroitUSA
  3. 3.Departments of PathologyWayne State UniversityDetroitUSA
  4. 4.Gershenson Radiation Oncology CenterHarper HospitalDetroitUSA
  5. 5.Laboratory for Chemical EnzymologyInstitute of Bioorganic ChemistryKievUkraine
  6. 6.Department of Medicine, Division of Hematology/OncologyDuke UniversityDurhamU.K.
  7. 7.First Institute of Pathology and Experimental Cancer ResearchSemmelweis Medical UniversityBudapestHungary
  8. 8.Deutsches KrebsforschungszentrumHeidelbergGermany

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