Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination.

Abstract

Metastases are the main cause of cancer-induced deaths worldwide. To block tissue invasion, development of extracellular vesicles (EVs) as therapeutic carriers, appears as an exciting challenge. To this aim, we took advantage of the anti-invasive function of NFAT3 transcription factor we identified previously in breast cancer and addressed the opportunity to transfer this inhibitory function by EVs. We show here that EVs produced by poorly invasive NFAT3-expressing breast cancer cell lines are competent to block in vitro invasion of aggressive cancer cells from different origins and, in cooperation with macrophages, inhibit cell proliferation and induce apoptosis. Moreover, this inhibitory effect can be improved by overexpression of NFAT3 in the EVs-producing cells. These results were extended in a mouse breast cancer model, with clear impact of inhibitory EVs on tumor growth and metastases spreading. This work identifies EVs produced by NFAT3-expressing breast cancer cells as an anti-tumoral tool to tackle cancer development and metastases dissemination.