Triple Negative (TN) breast tumours have poor prognosis, lack of targeted therapies and are often refractory to conventional chemotherapy treatments. Therefore, finding new therapeutic targets for those tumours is an unmet need with high clinical impact. In this context, Oncostatin M receptor (OSMR) is a promising therapeutic target as it is over-expressed in this tumour subtype and its activation promotes invasiveness1,2. We previously showed that OSMR is frequently copy-number gained and over-expressed in squamous cell carcinoma, where it induces migration, invasion and metastasis3,4,5. We now investigate the role of OSMR in breast cancer progression. 1. Guo L, et al. (2013) Oncogene 32: 5272–5282. 2. West NR, et al. (2014) Oncogene 33: 1485-1494 3. Caffarel MM, Coleman N. (2014) Journal of Pathology 232:386-90 4. Caffarel MM, et al (2013) Journal of Pathology 231:168-79 5. Kucia-Tran, et al. (2016) Brit J Cancer 115:212-222.
To address this issue we use a wide array of tools including in vitro cell cultures and in vivo models. The expression of OSMR pathway was analysed in FFPE samples and large datasets of publicly available breast cancer samples (METABRIC, n = 1462; and TCGA, n = 547).
OSMR and its ligand Oncostatin M (OSM) are over-expressed in basal tumours, where they associate with shorter overall survival (p = 0.015). While OSMR is expressed by breast cancer cells, the main source of OSM seems to be the tumour stroma, primarily cancer associated macrophages and fibroblasts. OSM treatment of breast cancer cells induces the expression of important mediators of angiogenesis and invasion. Importantly, OSMR activation accelerates tumour onset, tumour growth and metastasis in orthotopic xenografts in nude mice.
Our results support that OSMR pathway may have an important role in the initiation and progression of breast cancer and that it could be a promising candidate for therapeutic targeting in Triple Negative Breast Cancer. OSMR could be blocked by antibody based inhibition, strategy that has had a major impact on breast cancer.
Clinical trial identification
Legal entity responsible for the study
Molecular Oncology group, Biodonostia Health Research Institute
This work was funded by MINECO (PI15/00623) and Beca SEOM/FontVella 2015, and supported by Roche.
All authors have declared no conflicts of interest.