Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastais via P2Y₂ Receptor

Dagmar Schumacher D., Boris Strilic B., Kishor Kumar Sivaraj K. K., Nina Wettschureck N., and Stefan Offermanns S.

Cancer Cell (2013) 24, 130-137.

Speaker: Chi-Hua Lee (李季樺)                   Time: 15:00~16:00, Oct. 30, 2013.

Commentator: Dr. Guey-Chuen Perng (彭貴春老師博士)  Place: Room 601

Abstract:

Metastasis is responsible for most of the cancer death and cancer patients frequently presenting with signs of thrombosis become most more severe if the disease progressesed to a themetastatic stage [1]. Platelets, small and specialized blood cells, a small, disk shaped clear cell fragments, which are derived from fragmentation of precursor megakaryocytes. They participate in blood circulation, hemostasis and the formation of blood clots [2]. Various studies demonstrated that platelets are involved in tumor cell metastasis. In previous clinical studies, Rothwell et al.found that after long-term treatment with aspirin at an anti-platelet dosagee reduced the risk of cancer metastasis, which statedindicating the role of platelets in promoting tumor metastasis [3].And thisFurthermore, metastasis potential of tumor cells metastasis correlates with its ability to induce platelets activation. However,Despite the role of platelets and -tumor cell interaction in metastasis is well establishedstudied, but the underlying mechanism how thehow platelets promote the metastasis remains unclear. In this paper, the authors studied revealed the role of platelet secretion in endothelial transmigration of tumor cells during metastatic dissemination. They showed that adenine nucleiotides, a purine derivative that can form adenosine triphosphate (ATP),released from tumor cell-activated platelets induce opening of the endothelial barrier for tumor cell transendothelial migration and thereby promote cancer cell extravasation. Furthermore, they identified a metabotropic endothelial P2Y₂ receptor, which senses molecules outside the cell and activates inside signal transduction pathways and cellular responses. It can be activated activatedby ATP and is the primary mediator of promoting tumor cell metastasis in vitro. Moreover, they demonstrated that mice with P2Y₂ gene deficiency or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. In the endBased on above findings, the authors suggest propose that as a novel antimetastatic therapy, platelet secretion, endothelial P2Y₂ receptor and itstheir endothelial downstream signaling mechanisms pathway can be the potentiala targets for the prevention of cancer cell metastasisantimetastatic therapyies.

References:

1.     Gay L.aurie J. Gay and Brunhilde Felding-Habermann. B. F. (2011). Contribution of platelets to tumour metastasis. Nature Reviews Cancer. 11, 123-134.

•  (2008). Biology (8th ed.). London: Pearson Education. p.912.

3.      Rothwell, P. M., Wilson,  M., Price, J.F., Belch, J.F., Meade, T.W., and Mehta, Z. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomisedcontrolled trials. Lancet. 379, 1591–1601.