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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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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]
Total Authors: 9
[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
Total Affiliations: 6
Document type: Journal article
Source: FRONTIERS IN PHARMACOLOGY; v. 10, SEP 25 2019.
Web of Science Citations: 0

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)

FAPESP's process: 11/02144-4 - Involvement of “The knin B1 receptor ín melanoma development ánd metastasis
Grantee:Andrea Gutierrez Maria
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 10/13346-4 - Evaluation of the kinin B1 receptor role in melanoma growth
Grantee:Claudio Miguel da Costa Neto
Support type: Regular Research Grants
FAPESP's process: 12/20148-0 - Development of new ligands/drugs with selective agonism action (biased agonism) for receptors of the renin-angiotensin and kallikrein-kinin systems: new properties and new biotechnological applications
Grantee:Claudio Miguel da Costa Neto
Support type: Research Projects - Thematic Grants