Expression of PAFR as part of a prosurvival response to chemotherapy: a novel target for combination therapy in melanoma.

Mediators of Inflammation
Ana Claudia OnuchicRoger Chammas

Abstract

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.

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Citations

Feb 26, 2013·European Journal of Internal Medicine·Hadi A GoubranMagdy El-Ekiaby
Oct 10, 2015·FEBS Letters·Renata de Freitas SaitoRoger Chammas
Sep 30, 2014·Journal of Experimental & Clinical Cancer Research : CR·Yi YuCongjian Xu
Apr 30, 2015·Mediators of Inflammation·Ravi P SahuJeffrey B Travers
Mar 11, 2017·Nature Reviews. Cancer·Roger ChammasSonia Jancar
Feb 16, 2018·Journal of Immunology Research·Ildefonso Alves da Silva JuniorAna Paula Lepique
Aug 16, 2013·Journal of Biomolecular Screening·Stephen L Garland
May 2, 2017·Bioinorganic Chemistry and Applications·Vasiliki D PapakonstantinouAthanassios I Philippopoulos
Dec 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ronan LordanConstantinos A Demopoulos
Feb 21, 2018·Frontiers in Oncology·Ildefonso Alves da Silva-JuniorSonia Jancar
Aug 1, 2018·Nature Chemistry·Yusuke KurodaRichmond Sarpong
Apr 3, 2021·Frontiers in Endocrinology·Jeffrey B TraversRavi P Sahu
Jul 4, 2021·International Journal of Biological Macromolecules·Jenifer P GonçalvesCarolina C de Oliveira

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Methods Mentioned

BETA
PCR

Software Mentioned

Image
GraphPad Prism
Cell Quest Pro

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