Avaliação bioquímica do secretoma de células de adenocarcinoma de mama - MACL-1

Abstract

Breast cancer remains the second cause of death in women and the incidence of this disease is growing every year. In spite the large studies in vitro of breast cancer cell lines derived from non-metastatic tumors have been rarely reported whereas they may offer relevant data regarding stages of tumor development and contribute to a better understanding of pathophysiology. The components studies produced and secreted (secretoma) by the tumor cells demonstrated their contribution to process of tumorigenesis in several types of cancer, such breast and prostate. However, MACL-1 cells secretome activity on nontumor cells has not been investigated and components are still poorly described. Then, CCD19-Lu fibroblasts were exposed of MACL-1 cells secretome and we evaluated changes in morphology, proliferation rate, protein expression and reactive oxygen species (ROS) production. Co-cultures in Transwells assays showed that, when exposed to MACL-1 cells secretome, CCD19-Lu cells had their morphology and proliferation rate altered and an increased in Vimentin, fibroblast activation protein (FAP), nuclear transcription factor NFκB, proteases and IL-6 expression. These results suggested a phenotype changes of cells and proteomic analyzes identified proteins specific activity to increase of ROS production by CCD19-Lu cells exposed MACL-1 cells secretome establish a direct correlation with the phenotypic alterations observed in fibroblasts. Thus, we suggest that MACL-1 cells from a primary breast tumor secrete proteins with biochemical activities capable of altering CCD19-Lu fibroblasts phenotype leading to modifications mainly in the proteins expression point to a possible transformation of these cells into cancer associated fibroblasts (CAFs).