Activation of the Kinin B1 Receptor by Its Agonist Reduces Melanoma Metastasis by Playing a Dual Effect on Tumor Cells and Host Immune Response

• Published in: Frontiers in pharmacology Vol. 10; p. 1106
• Main Authors: Maria, Andrea Gutierrez, Dillemburg-Pilla, Patrícia, Durand, Marina de Toledo, Floriano, Elaine Medeiros, Manfiolli, Adriana Oliveira, Ramos, Simone Gusmão, Pesquero, João Bosco, Nahmias, Clara, Costa-Neto, Claudio M.
• Format: Journal Article
• Language: English
• Published: Frontiers 25.09.2019; Frontiers Media S.A
• Subjects: Animal biology; B1 receptor; Cancer; des-Arg9-bradykinin; immune response; inflammation; Life Sciences; melanoma; Pharmaceutical sciences; Pharmacology; tumor microenvironment
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2019.01106

Metastatic melanoma is an aggressive type of skin cancer leading half of the patients todeath within 8–10 months after diagnosis. Kinins are peptides that interact with B1 andB2 receptors playing diverse biological roles. We investigated whether treatment with B1receptor agonist, des-Arg9-bradykinin (DABK), has effects in lung metastasis establishmentafter melanoma induction in mice. We found a lower number of metastatic colonies in lungsof 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 animalsthat did not receive treatment. To understand whether the effects of DABK observedwere due to the activation of the B1 receptor in the tumor cells or in the host, we treatedwild-type (WT) and kinin B1 receptor knockout (B1−/−) mice with DABK. No significantdifferences in the number of melanoma colonies established in lungs were seen betweenWT and B1−/−mice; however, B1−/−mice presented higher VCAM-1 expression and lowerCD8+T-cell infiltration. In conclusion, we believe that activation of kinin B1 receptor by itsagonist in the host stimulates the immune response more efficiently, promoting CD8+Tcellrecruitment to the metastatic lungs and interfering in VCAM-1 expression. Moreover,treatment with DABK reduced establishment of metastatic colonies by mainly actingon tumor cells; hence, this study brings insights to explore novel approaches to treatmetastatic melanoma targeting the B1 receptor.