Abstract C289: The kinin B1 receptor enhances the host protective response against murine melanoma aggressiveness.

The incidence of malignant melanoma has significantly increased in the last few decades and advanced cases of this disease are still resistant to all types of therapies and represent a therapeutic challenge. Tumor development and growth depend on alterations that lead to an unlimited replicative potential, evasion of apoptosis and escape from immune response and also, on a permissive microenvironment. Chronic and persistent inflammation may also contribute to cancer development, and the relationship between the kinin B1 receptor and inflammation is well established. Furthermore, previous studies have shown that the kinin B1 receptor attenuates primary melanoma and metastasis. In this study, we show the role of the B1 receptor in the host tumor microenvironment during melanoma progression. To investigate this phenomenon, we inoculated B16F10 cells in wild type and B1 receptor-knockout mice, tumors were removed and several approaches were evaluated such as proliferation and cell survival pathways by western blotting, vascularization and mitosis by histology and cytokines expression levels by real time PCR. Our results show that the presence of the B1 receptor in the microenvironment did not represent a significant factor to modulate tumor size and time of appearance. Nevertheless, molecular analysis revealed that the lack of the B1 receptor resulted in development of tumors with more aggressive features. The melanomas that developed in the B1 receptor-knockout mice had the same vascularization as melanomas developed in the wild type animals but presented higher number of cells in mitosis, and the proliferative signaling pathways in the B1 receptor-knockout tumors were more strongly activated. Likewise, these tumors had lower levels of p38 and JNK activation, and higher levels of IL-10. Additionally, the tumors that developed in the B1 receptor-knockout mice were able to disrupt the skin near the tumor area. Taken together, our results suggest that the B1 receptor has an important role in supporting the host immune response against melanoma aggressiveness. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C289. Citation Format: Andrea G. Maria, Patricia Dillenburg-Pilla, Rosana Inacio dos Reis, Elaine Floriano Medeiros, Cristiane Tefe-Silva, Simone Gusmao Ramos, Joao Bosco Pesquero, Claudio Miguel Costa-Neto. The kinin B1 receptor enhances the host protective response against murine melanoma aggressiveness. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C289.