Histamine action in tumor microenvironment

PORRETTI J, MOHAMAD N, ESNAOLA M, BADENAS M, RIVERA E, MARTÍN G, CRICCO G.

MENDOZA

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Tumor microenvironment is composed of immune and endothelial cells, fibroblasts and extracellular matrix. Interactions between tumor cells and stroma are crucial for cell growth regulation and tumor metastasis. Previously we demonstrated that histamine (HA) modified epithelial to mesenchymal transition (EMT), required to change a benign tumor in an aggressive and invasive cancer. Our aim was to evaluate HA action in the interaction between the human mammary tumor cells MDA MB-231 and the normal fibroblasts CCD-1059SK. We obtained the conditioned media (CM) from fibroblasts treated or not with two doses of HA (0.1 and 20 uM). Tumor cells cultivated with CM from control fibroblasts showed an increase in the expression of the mesenchymal marker smooth muscle alpha actin by flow cytometry, in MMP9 activity by zymography and in the migratory capacity by transwells. A decrease in the expression of the epithelial marker E cadherin was observed by western blot. The levels of phosphorylation/activation of c-Src, related to cell migration, were also increased. However these effects were reverted when MDA MB-231 cells were grown with CM from 20uM HA treated fibroblasts. A diminution was also found in mRNA steady sate levels of Slug, a known inducer of EMT. These results signal HA capacity of modifying tumor microenvironment and open a perspective for the design of therapies in the future.