NDLI: Melanoma cell metastasis via P-selectin-mediated activation of acid sphingomyelinase in platelets

Content Provider	Springer Nature Link
Author	Becker, Katrin Anne Beckmann, Nadine Adams, Constantin Hessler, Gabriele Kramer, Melanie Gulbins, Erich Carpinteiro, Alexander
Copyright Year	2016
Abstract	Metastatic dissemination of cancer cells is one of the hallmarks of malignancy and accounts for approximately 90 % of human cancer deaths. Within the blood vasculature, tumor cells may aggregate with platelets to form clots, adhere to and spread onto endothelial cells, and finally extravasate to form metastatic colonies. We have previously shown that sphingolipids play a central role in the interaction of tumor cells with platelets; this interaction is a prerequisite for hematogenous tumor metastasis in at least some tumor models. Here we show that the interaction between melanoma cells and platelets results in rapid and transient activation and secretion of acid sphingomyelinase (Asm) in WT but not in P-selectin-deficient platelets. Stimulation of P-selectin resulted in activation of p38 MAPK, and inhibition of p38 MAPK in platelets prevented the secretion of Asm after interaction with tumor cells. Intravenous injection of melanoma cells into WT mice resulted in multiple lung metastases, while in P-selectin-deficient mice pulmonary tumor metastasis and trapping of tumor cells in the lung was significantly reduced. Pre-incubation of tumor cells with recombinant ASM restored trapping of B16F10 melanoma cells in the lung in P-selectin-deficient mice. These findings indicate a novel pathway in tumor metastasis, i.e., tumor cell mediated activation of P-selectin in platelets, followed by activation and secretion of Asm and in turn release of ceramide and tumor metastasis. The data suggest that p38 MAPK acts downstream from P-selectin and is necessary for the secretion of Asm.
Starting Page	25
Ending Page	35
Page Count	11
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	34
Issue Number	1
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-10-15
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	P-selectin Acid sphingomyelinase Ceramide p38 MAPK Platelets Metastasis Cancer Research Biomedicine Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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