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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 by Its Agonist Reduces Melanoma Metastasis by Playing a Dual Effect on Tumor Cells and Host Immune Response

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Autor(es):
Maria, Andrea Gutierrez [1, 2] ; Dillemburg-Pilla, Patricia [1] ; Durand, Marina de Toledo [3] ; Floriano, Elaine Medeiros [4] ; Manfiolli, Adriana Oliveira [1] ; Ramos, Simone Gusmao [4] ; Pesquero, Joao Bosco [5] ; Nahmias, Clara [6] ; Costa-Neto, Claudio M. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Genet & Endocrinol, Bethesda, MD 20892 - USA
[3] Univ Ribeirao Preto, Dept Med, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto - Brazil
[5] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil
[6] Gustave Roussy Canc Ctr, Dept Mol Med, INSERM, U981, Villejuif - France
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN PHARMACOLOGY; v. 10, SEP 25 2019.
Citações Web of Science: 0
Resumo

Metastatic melanoma is an aggressive type of skin cancer leading half of the patients to death within 8-10 months after diagnosis. Kinins are peptides that interact with B1 and B2 receptors playing diverse biological roles. We investigated whether treatment with B1 receptor agonist, des-Arg(9)-bradykinin (DABK), has effects in lung metastasis establishment after melanoma induction in mice. We found a lower number of metastatic colonies in lungs of DABK-treated mice, reduced expression of vascular cell adhesion molecule 1 (VCAM-1), and increased CD8(+)T-cell recruitment to the metastatic area compared to animals that did not receive treatment. To understand whether the effects of DABK observed were due to the activation of the B1 receptor in the tumor cells or in the host, we treated wild-type (WT) and kinin B1 receptor knockout (B1(-/-)) mice with DABK. No significant differences in the number of melanoma colonies established in lungs were seen between WT and B1(-/-)mice; however, B1(-/-)mice presented higher VCAM-1 expression and lower CD8(+)T-cell infiltration. In conclusion, we believe that activation of kinin B1 receptor by its agonist in the host stimulates the immune response more efficiently, promoting CD8(+)T-cell recruitment to the metastatic lungs and interfering in VCAM-1 expression. Moreover, treatment with DABK reduced establishment of metastatic colonies by mainly acting on tumor cells; hence, this study brings insights to explore novel approaches to treat metastatic melanoma targeting the B1 receptor. (AU)

Processo FAPESP: 11/02144-4 - Envolvimento do receptor B1 de cininas no desenvolvimento de melanoma e metástase
Beneficiário:Andrea Gutierrez Maria
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 12/20148-0 - Desenvolvimento de novos ligantes/drogas com ação agonística seletiva ("biased agonism") para receptores dos sistemas renina-angiotensina e calicreínas-cininas: novas propriedades e novas aplicações biotecnológicas
Beneficiário:Claudio Miguel da Costa Neto
Linha de fomento: Auxílio à Pesquisa - Temático
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