Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma
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 incr...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/175408 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849402290692161536 |
|---|---|
| author | Ana Claudia Onuchic Camila M. L. Machado Renata F. Saito Francisco J. Rios Sônia Jancar Roger Chammas |
| author_facet | Ana Claudia Onuchic Camila M. L. Machado Renata F. Saito Francisco J. Rios Sônia Jancar Roger Chammas |
| author_sort | Ana Claudia Onuchic |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8aa04f38fab0402cba2eb14a3618bc06 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-8aa04f38fab0402cba2eb14a3618bc062025-08-20T03:37:34ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/175408175408Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in MelanomaAna Claudia Onuchic0Camila M. L. Machado1Renata F. Saito2Francisco J. Rios3Sônia Jancar4Roger Chammas5Departamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, SP, BrazilDepartamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, SP, BrazilDepartamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-900 São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-900 São Paulo, SP, BrazilDepartamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, 01246-903 São Paulo, SP, BrazilMelanoma 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.http://dx.doi.org/10.1155/2012/175408 |
| spellingShingle | Ana Claudia Onuchic Camila M. L. Machado Renata F. Saito Francisco J. Rios Sônia Jancar Roger Chammas Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma Mediators of Inflammation |
| title | Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma |
| title_full | Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma |
| title_fullStr | Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma |
| title_full_unstemmed | Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma |
| title_short | Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma |
| title_sort | expression of pafr as part of a prosurvival response to chemotherapy a novel target for combination therapy in melanoma |
| url | http://dx.doi.org/10.1155/2012/175408 |
| work_keys_str_mv | AT anaclaudiaonuchic expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma AT camilamlmachado expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma AT renatafsaito expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma AT franciscojrios expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma AT soniajancar expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma AT rogerchammas expressionofpafraspartofaprosurvivalresponsetochemotherapyanoveltargetforcombinationtherapyinmelanoma |