Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Basic science

3566 - New targets in Triple Negative Breast Cancer: Role of Oncostatin M receptor pathway

Date

10 Sep 2017

Session

Basic science

Presenters

Maria Muñoz Caffarel

Citation

Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361

Authors

M. Muñoz Caffarel1, A. Araujo1, C. Lawrie1, I. Álvarez López2, R. Rezola3, A. Abaurrea1

Author affiliations

  • 1 Oncologia, Asociación Instituto Biodonostia, 20014 - San Sebastian/ES
  • 2 Medical Oncology, Hospital Universitario Donostia, 20014 - Donostia/ES
  • 3 Department Of Pathology And Anatomy, Onkologikoa, San Sebastian/ES
More

Resources

Abstract 3566

Background

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.

Methods

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).

Results

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.

Conclusions

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

Funding

This work was funded by MINECO (PI15/00623) and Beca SEOM/FontVella 2015, and supported by Roche.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.