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Platelets, autotaxin and lysophosphatidic acid signalling: win‐win factors for cancer metastasis
Author(s) -
Leblanc Raphael,
Houssin Audrey,
Peyruchaud Olivier
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14362
Subject(s) - autotaxin , lysophosphatidic acid , platelet , metastasis , cancer cell , biology , cancer research , cancer , microbiology and biotechnology , medicine , immunology , biochemistry , receptor
Platelets play a crucial role in the survival of metastatic cells in the blood circulation. The interaction of tumour cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA), because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation, and blocking platelet function decreases LPA signalling and leads to inhibition of breast cancer cell metastasis. Autotaxin (ATX), a lysophospholipase D responsible for the basal concentration of LPA in blood, was detected in platelet α‐granules. Functionally, active ATX is eventually released following tumour cell‐induced platelet aggregation, thereby promoting metastasis. Megakaryocytes do not express ATX but respond to LPA stimulation. Whether LPA‐primed megakaryocytes contribute to the recently reported negative action of megakaryocytes on cancer metastasis is not yet known. However, an understanding of the ATX/LPA signalling pathways in platelets, cancer cells and megakaryocytes opens up new approaches for fighting cancer metastasis.