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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Activation of the Kinin B1 Receptor Attenuates Melanoma Tumor Growth and Metastasis

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Autor(es):
Dillenburg-Pilla, Patricia [1] ; Maria, Andrea G. [1] ; Reis, Rosana I. [1] ; Floriano, Elaine Medeiros [2] ; Pereira, Cacilda Dias [1] ; De Lucca, Fernando Luiz [1] ; Ramos, Simone Gusmao [2] ; Pesquero, Joao B. [3] ; Jasiulionis, Miriam G. [4] ; Costa-Neto, Claudio M. [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med, Dept Biochem & Immunol, BR-14049 Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Pathol, BR-14049 Ribeirao Preto - Brazil
[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 8, n. 5 MAY 17 2013.
Citações Web of Science: 6
Resumo

Melanoma is a very aggressive tumor that does not respond well to standard therapeutic approaches, such as radio-and chemotherapies. Furthermore, acquiring the ability to metastasize in melanoma and many other tumor types is directly related to incurable disease. The B1 kinin receptor participates in a variety of cancer-related pathophysiological events, such as inflammation and angiogenesis. Therefore, we investigated whether this G protein-coupled receptor plays a role in tumor progression. We used a murine melanoma cell line that expresses the kinin B1 receptor and does not express the kinin B2 receptor to investigate the precise contribution of activation of the B1 receptor in tumor progression and correlated events using various in vitro and in vivo approaches. Activation of the kinin B1 receptor in the absence of B2 receptor inhibits cell migration in vitro and decreases tumor formation in vivo. Moreover, tumors formed from cells stimulated with B1-specific agonist showed several features of decreased aggressiveness, such as smaller size and infiltration of inflammatory cells within the tumor area, higher levels of pro-inflammatory cytokines implicated in the host anti-tumor immune response, lower number of cells undergoing mitosis, a poorer vascular network, no signs of invasion of surrounding tissues or metastasis and increased animal survival. Our findings reveal that activation of the kinin B1 receptor has a host protective role during murine melanoma tumor progression, suggesting that the B1 receptor could be a new anti-tumor GPCR and provide new opportunities for therapeutic targeting. (AU)

Processo FAPESP: 06/61810-6 - Acões pleiotrópicas dos sistemas renina-angiotensina e calicreínas-cininas
Beneficiário:Claudio Miguel da Costa Neto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/13346-4 - Avaliação do papel do receptor B1 de cininas no desenvolvimento de melanoma
Beneficiário:Claudio Miguel da Costa Neto
Linha de fomento: Auxílio à Pesquisa - Regular