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Cyclooxygenases and lipoxygenases in cancer

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Abstract

Cancer initiation and progression are multistep events that require cell proliferation, migration, extravasation to the blood or lymphatic vessels, arrest to the metastatic site, and ultimately secondary growth. Tumor cell functions at both primary or secondary sites are controlled by many different factors, including growth factors and their receptors, chemokines, nuclear receptors, cell–cell interactions, cell–matrix interactions, as well as oxygenated metabolites of arachidonic acid. The observation that cyclooxygenases and lipoxygenases and their arachidonic acid-derived eicosanoid products (prostanoids and HETEs) are expressed and produced by tumor cells, together with the finding that these enzymes can regulate cell growth, survival, migration, and invasion, has prompted investigators to analyze the roles of these enzymes in cancer progression. In this review, we focus on the contribution of cyclooxygenase- and lipoxygenase-derived eicosanoids to tumor cell function in vitro and in vivo and discuss hope and tribulations of targeting these enzymes for cancer prevention and treatment.

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Abbreviations

COX:

Cyclooxygenase

LOX:

Lipoxygenase

PGE2 :

Prostaglandin E2

PGI2 :

Prostacyclin

PGF2α :

Prostaglandin F2α

TxA2 :

Thromboxane A2

EP:

Prostaglandin E receptor

HK:

Cyclic hemiketal eicosanoid

NSAID:

Nonsteroidal anti-inflammatory drug

LTB4 :

Leukotriene B4

HODE:

Hydroxyoctadecadienoic acid

PGD2 :

Prostaglandin D2

VEGF:

Vascular endothelial growth factor

NF-κB:

Nuclear factor-kappaB

PI3K/Akt:

Phospatidylinositol-3-kinase/Akt

PPAR:

Peroxisome proliferator-activated receptor

TNF:

Tumor necrosis factor

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Acknowledgments

These studies were in part supported by a Merit Review from the Department of Veterans Affairs (AP) and the NIH grants 2P01DK065123 (AP); 2PO1DK38226 (AP); the O’Brien P30DK79341-01 (AP); and GM076592 (CS).

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Authors and Affiliations

  1. Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN, 37232, USA

    Claus Schneider

  2. Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN, 37232, USA

    Claus Schneider

  3. Department of Medicine, Vanderbilt University Medical School, Nashville, TN, 37232, USA

    Ambra Pozzi

  4. Department of Cancer Biology, Vanderbilt University Medical School, Nashville, TN, 37232, USA

    Ambra Pozzi

  5. Veterans Affairs Hospitals, Nashville, TN, 37215, USA

    Ambra Pozzi

  6. Departments of Medicine and Cancer Biology, Division of Nephrology and Hypertension, Vanderbilt University, Medical Center North, B3115, Nashville, TN, 37232, USA

    Ambra Pozzi

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  1. Claus Schneider
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  2. Ambra Pozzi
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Correspondence to Ambra Pozzi.

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Schneider, C., Pozzi, A. Cyclooxygenases and lipoxygenases in cancer. Cancer Metastasis Rev 30, 277–294 (2011). https://doi.org/10.1007/s10555-011-9310-3

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  • DOI: https://doi.org/10.1007/s10555-011-9310-3

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