Angela Araujo. Grupo Cáncer de mama, IIS Biodonostia.
Dr. Charles Lawrie y Dra. Maria Caffarel.
Cytokines are key players in inflammation, a process associated with tumour initiation, angiogenesis and metastasis. However, the interplay between inflammation and other cell types in the tumour microenvironment is not well understood. In our work we show that the IL6-related proinflammatory cytokine Oncostatin M (OSM) is a central node for multicellular interactions. Myeloid-derived OSM reprogrammes CAFs and cancer cells, promoting breast cancer progression. In addition, OSM induces the secretion of inflammatory cytokines and chemokines from CAFs and cancer cells, which in turn reinforce myeloid tumour infiltration. OSM is increased in cancer stroma and is associated with poor prognosis in multiple cancer types. Abrogation of OSM signalling in a multistage breast cancer mouse model delays tumour onset, tumour growth and reduces metastatic burden. Our results reveal an unprecedented tumour promoting paracrine OSM: OSMR signalling crosstalk encompassing myeloid cells, CAFs and tumour cells, thus encouraging therapeutic strategies aimed at targeting this oncogenic axis in breast cancer.
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