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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorONUCHIC, Ana Claudia
dc.contributor.authorMACHADO, Camila M. L.
dc.contributor.authorSAITO, Renata F.
dc.contributor.authorRIOS, Francisco J.
dc.contributor.authorJANCAR, Sonia
dc.contributor.authorCHAMMAS, Roger
dc.date.accessioned2013-07-30T15:20:14Z
dc.date.available2013-07-30T15:20:14Z
dc.date.issued2012
dc.description.abstractMelanoma 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [1998/14247-6, 2008/00247-8]
dc.identifier.citationMEDIATORS OF INFLAMMATION, article ID 175408, 6p, 2012
dc.identifier.doi10.1155/2012/175408
dc.identifier.issn0962-9351
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1134
dc.language.isoeng
dc.publisherHINDAWI PUBLISHING CORPORATION
dc.relation.ispartofMediators of Inflammation
dc.rightsopenAccess
dc.rights.holderCopyright HINDAWI PUBLISHING CORPORATION
dc.subject.otherplatelet-activating-factor
dc.subject.otherbreast-cancer cells
dc.subject.otherfactor receptor
dc.subject.othergrowth
dc.subject.otherangiogenesis
dc.subject.otherapoptosis
dc.subject.wosCell Biology
dc.subject.wosImmunology
dc.titleExpression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalRIOS, Francisco J.:Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil
hcfmusp.author.externalJANCAR, Sonia:Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil
hcfmusp.citation.scopus36
hcfmusp.contributor.author-fmusphcANA CLAUDIA ONUCHIC
hcfmusp.contributor.author-fmusphcCAMILA MARIA LONGO MACHADO
hcfmusp.contributor.author-fmusphcRENATA DE FREITAS SAITO
hcfmusp.contributor.author-fmusphcROGER CHAMMAS
hcfmusp.description.articlenumber175408
hcfmusp.description.volume2012
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed22570511
hcfmusp.origem.scopus2-s2.0-84861029935
hcfmusp.origem.wosWOS:000303707400001
hcfmusp.publisher.cityNEW YORK
hcfmusp.publisher.countryUSA
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hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.scopus.lastupdate2024-05-17
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