Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Author(s)

Onuchic, Ana Claudia ; Machado, Camila M. L. ; Saito, Renata F. ; Rios, Francisco J. ; Jancar, Sonia ; Chammas, Roger

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2012, p. 6-pg., 2012-01-01.

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. (AU)

• FAPESP's process: 08/00247-8 - Cytometric assessment of the murine melanoma microenvironment in the course of experimental chemotherapy: analysis of inflammatory infiltrate and kinetics of tumor cell repopulation.
• Grantee: Ana Cláudia Onuchic
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 98/14247-6 - Center for Research on Cell-Based Therapy
• Grantee: Marco Antonio Zago
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC