Cancer and Metastasis Reviews

, Volume 37, Issue 2–3, pp 439–454 | Cite as

Bioactive lipid metabolism in platelet “first responder” and cancer biology

  • Preeti Kanikarla-Marie
  • Scott Kopetz
  • Ernest T. Hawk
  • Steven W. Millward
  • Anil K. Sood
  • Paolo Gresele
  • Michael Overman
  • Kenneth Honn
  • David G. MenterEmail author


Platelets can serve as “first responders” in cancer and metastasis. This is partly due to bioactive lipid metabolism that drives both platelet and cancer biology. The two primary eicosanoid metabolites that maintain platelet rapid response homeostasis are prostacyclin made by endothelial cells that inhibits platelet function, which is counterbalanced by thromboxane produced by platelets during activation, aggregation, and platelet recruitment. Both of these arachidonic acid metabolites are inherently unstable due to their chemical structure. Tumor cells by contrast predominantly make more chemically stable prostaglandin E2, which is the primary bioactive lipid associated with inflammation and oncogenesis. Pharmacological, clinical, and epidemiologic studies demonstrate that non-steroidal anti-inflammatory drugs (NSAIDs), which target cyclooxygenases, can help prevent cancer. Much of the molecular and biological impact of these drugs is generally accepted in the field. Cyclooxygenases catalyze the rate-limiting production of substrate used by all synthase molecules, including those that produce prostaglandins along with prostacyclin and thromboxane. Additional eicosanoid metabolites include lipoxygenases, leukotrienes, and resolvins that can also influence platelets, inflammation, and carcinogenesis. Our knowledge base and technology are now progressing toward identifying newer molecular and cellular interactions that are leading to revealing additional targets. This review endeavors to summarize new developments in the field.


Platelets Cancer Metastasis Thromboxane Prostacyclin Prostaglandin Cyclooxygenase NSAID COXIB Aspirin 



15-Hydroxyprostaglandin Dehydrogenase


Activating Protein


Adenomatous polyposis coli


Arachidonic Acid


ATP-Binding Cassette


C-C motif Ligand 2


Cardiovascular disease


Colorectal cancer


Confidence interval (95%)


Cyclooxygenase inhibitors






Dendritic Cells


DNA methyl transferase


Docosahexaenoic acid


Eicosapentaenoic acid


Extracellular signal regulated kinase


Familial adenomatous polyposis






Hazard Ratio


Hydroxyeicosatetraenoic acid


Inhibitor of nuclear factor of kappa light chain in B-cells


Leukotriene B4




Microsatellite instability


Myeloid-derived suppressor cells


Natural killer


Non-steroidal anti-inflammatory drugs


Odds ratio


Organic ion transporter protein expression


PG transporter


PGE2 synthases, cytosolic/microsomal


PGI2 synthase




Phosphoinositide-dependent kinase-1


Phospholipase A2


Polymorphonuclear cells




Prostaglandin (prostanoid) E receptors


Prostaglandin E metabolite


Prostaglandin E2


Prostaglandin H2


Randomized controlled trial


Relative risk


T-cell receptor


Thromboxane synthase




Toll-like receptors


Tumor necrosis factor


Voltage-dependent anion channels



Grant and Other Support: Boone Pickens Distinguished Chair for Early Prevention of Cancer, Duncan Family Institute, Colorectal Cancer Moon Shot, 1R01CA187238-01, 5R01CA172670-03 and 1R01CA184843-01A1, CA177909, and the American Cancer Society Research Professor Award, Cancer Center Support Grant (P30 CA016672).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Preeti Kanikarla-Marie
    • 1
  • Scott Kopetz
    • 1
  • Ernest T. Hawk
    • 2
  • Steven W. Millward
    • 3
  • Anil K. Sood
    • 4
    • 5
    • 6
  • Paolo Gresele
    • 7
  • Michael Overman
    • 1
  • Kenneth Honn
    • 8
    • 9
    • 10
    • 11
  • David G. Menter
    • 1
    Email author
  1. 1.Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Office of the Vice President Cancer Prevention and Population ScienceThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Cancer Systems ImagingThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Gynocologic Oncology and Reproductive MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Center for RNA Interference and Non-Coding RNAThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of Medicine, Section of Internal and Cardiovascular MedicineUniversity of PerugiaPerugiaItaly
  8. 8.Bioactive Lipids Research Program, Department of PathologyWayne State UniversityDetroitUSA
  9. 9.Department of PathologyWayne State University School of MedicineDetroitUSA
  10. 10.Cancer Biology DivisionWayne State University School of MedicineDetroitUSA
  11. 11.Department of Gastrointestinal Medical OncologyM. D. Anderson Cancer CenterHoustonUSA

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