Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone
作者： Raphael Leblanc , Sue-Chin Lee , Marion David , Jean-Claude Bordet , Derek D. Norman
DOI: 10.1182/BLOOD-2014-04-568683
关键词: Metastasis 、 Integrin alphaVbeta3 、 Lysophosphatidic acid 、 Internal medicine 、 Cancer research 、 Platelet activation 、 Biology 、 Cancer 、 Cancer cell 、 Endocrinology 、 Integrin 、 Autotaxin
摘要: Autotaxin (ATX), through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed multiple types cancers, and together with LPA generated during platelet activation promotes skeletal metastasis breast cancer. However, the pathophysiological sequelae regulated interactions between circulating LPA, ATX, platelets remain undefined In this study, we show that stored α-granules resting human released upon tumor cell-induced aggregation, leading to production LPA. Our vitro vivo experiments using cancer cells do not express (MDA-MB-231 MDA-B02) demonstrate nontumoral early stage bone colonization by cells. Moreover, expression a dominant negative integrin αvβ3-Δ744 or treatment anti-human αvβ3 monoclonal antibody LM609, completely abolished binding cells, demonstrating requirement fully active process. The present results establish new mechanism for contribution LPA-dependent therapeutic potential disrupting nontumor-derived prevention metastasis.
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