Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity

Claudio Tripodo, Alessandro Gulino, Paola Portararo, Alessandra Santangelo, Nadia Castioni, Laura Botti, Sabina Sangaletti, Barbara Cappetti, Claudia Chiodoni, Mariella Parenza, Elda Tagliabue, Rosaria Orlandi, Mario P. Colombo

Risultato della ricerca: Article

37 Citazioni (Scopus)

Abstract

The extracellular matrix (ECM) contributes to the biological and clinical heterogeneity of breast cancer, and different prognostic groups can be identified according to specific ECM signatures. In high-grade, but not low-grade, tumors, an ECM signature characterized by high SPARC expression (ECM3) identifies tumors with increased epithelial-to-mesenchymal transition (EMT), reduced treatment response, and poor prognosis. To better understand how this ECM3 signature is contributing to tumorigenesis, we expressed SPARC in isogenic cell lines and found that SPARC overexpression in tumor cells reduces their growth rate and induces EMT. SPARC expression also results in the formation of a highly immunosuppressive microenvironment, composed by infiltrating T regulatory cells, mast cells, and myeloid-derived suppressor cells (MDSCs). The ability of SPARC to induce EMT depended on the localization and suppressive function of myeloid cells, and inhibition of the suppressive function MDSCs by administration of aminobisphosphonates could revert EMT, rendering SPARC-overexpressing tumor cells sensitive to Doxil. We conclude that that SPARC is regulating the interplay between MDSCs and the ECM to drive the induction of EMT in tumor cells.
Lingua originaleEnglish
pagine (da-a)233-248
Numero di pagine16
RivistaCell Reports
Volume17
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Entra nei temi di ricerca di 'Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity'. Insieme formano una fingerprint unica.

  • Cita questo

    Tripodo, C., Gulino, A., Portararo, P., Santangelo, A., Castioni, N., Botti, L., Sangaletti, S., Cappetti, B., Chiodoni, C., Parenza, M., Tagliabue, E., Orlandi, R., & Colombo, M. P. (2016). Mesenchymal Transition of High-Grade Breast Carcinomas Depends on Extracellular Matrix Control of Myeloid Suppressor Cell Activity. Cell Reports, 17, 233-248.