Stromal cytokine signalling promotes breast cancer progression by reprograming the tumor microenvironment
María Muñoz Caffarel
del Instituto de Investigación Sanitaria Biodonostia/ Hospital Donostia de San Sebastián
The tumour microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumour progression. The contribution of stromal cells to the reprogramming of the TME is not well-understood. Our laboratory has recently identified the cytokine Oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. Oncostatin M Receptor (OSMR) deletion in a multistage breast cancer model halts tumour progression. We ascribed causality to the stromal function of OSM axis by demonstrating reduced tumour burden of syngeneic tumours implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumours revealed that OSM expression is restricted to myeloid cells, whereas OSMR is detected predominantly in fibroblasts and, to a lower extent, cancer cells. Collectively, our data support that stromal OSM:OSMR axis reprograms the immune and non-immune microenvironment and plays a key role in breast cancer progression.
During this talk, I will present these results and other projects from the laboratory including the involvement of cytokine signalling in hypoxia, integrin signalling, ECM remodelling and metastasis.