The Kinin B1 Receptor induces the expression and secretion of IL-10 and M-CSF from breast cancer cells, favoring the differentiation and migration of macrophages

María Francisca Pavicic¹, Carola Matus², Iraidi Ramos¹, Carlos Dario Figueroa¹, Pamela Ehrenfeld¹, ³

The tumor microenvironment consists of a strong interaction between various cell types and molecular factors such as cytokines, growth factors, and proteases, which are intended to favor tumor progression. Kinins such as Lys-des[Arg9] bradykinin (LDBK) are key modulators that exert their effects by stimulating the kinin B1 receptor (B1R). Among the cells that compose tumor microenvironment are macrophages, which in a milieu rich in IL-10 and/or monocyte colony-stimulating factor (M-CSF) can be differentiated in a protumoral, M2 phenotype. Our aim was to determine if the stimulation of B1R with LDBK induces the expression and/or secretion of IL-10 and M-CSF in breast cancer cells and if their conditioned media (CM) induces macrophage migration and/or differentiation. For this, cells were stimulated with LDBK and the protein expression and secretion of IL-10 and M-CSF, in cell extracts and CM was determined by protein microarray and/or western blotting. In addition, was determine that THP1 macrophages stimulated with CM from breast cancer cells boosted migration and expression of several differentiation markers. Our results demostrate that B1R activation in breast cancer cells induces the expression and/or secretion of IL-10 and M-CSF. Also, it could favor macrophage migratory capacity during tumor progression.

Acknowledgments: Instituto de Anatomia, Histología y Patología, VIDCA, Fondecyt 1201635, Escuela de Graduados, Facultad de Medicina