Tumor Microenvironment Induces c-Fos Overexpression and Breast Cancer Stem Cells Enrichment

CASTELLARO AM; CAPUTTO BL; GIL GA.

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual de SAIB; 2011

The Epithelial Mesenchimal Transition (EMT) program depends on a series of intracellular signaling networks involving, among others signal-transduction proteins, ERK, MAPK, PI3K, and c- Fos. Induction of c-Fos expression in normal mouse mammary epithelial cells induces EMT and is associated with a decrease in Ecadherin expression. Previous to EMT, CD44-/CD24+ cells correspond to the phenotype of the majority of cells found in breast carcinomas whereas a shift to CD44+/CD24- cells, promotes EMT and a profile associated with human breast cancer stem cells leading to the acquisition of mesenchymal qualities and an increased ability to form mammospheres and increased metastatic potential. We found, that the microenvironment formed by macrophages induces both EMT in breast cancer cells with a stem cell?like phenotype and overexpression of c-Fos. Furthermore, in cultures, this microenvironment induces proliferation, invasiveness; and migration of these breast cancer cells. In vivo, this microenvironment increases breast tumor growth when macrophages are co-injected with MCF-7 cells into immunocompromised mice.