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.
Highlights
Metastases are the main cause of cancer-induced deaths worldwide
Having shown that NFAT3, significantly more expressed in luminal breast cancer, inhibits breast cancer cell invasion[9], we evaluate here the possibility that extracellular vesicles (EVs) produced by luminal breast cancer cells might be competent to transfer this inhibitory capacity by NFAT3 to triple negative breast cancer cells lines
These results demonstrate for the first time the specificity and capacity of EVs produced by luminal breast cancer cells to inhibit the invasion of highly aggressive triple negative breast cancer counterparts
Summary
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. If EVs have been proposed as biomarkers of cancer progression and associated with a pro-tumoral role[3,4], they represent an attractive alternative to cell therapy, with possible genetic and trophic material transfer to receptor cells, without the risks inherent to the injection of whole living cells To this end, EVs have already been tested in humans through phase I and II clinical trials, demonstrating safety in variable indications[1]. Based on EVs knowledge and on our previous work on NFAT functional roles in metastasis, we aimed to transfer the anti-invasive properties of NFAT3 isotype to tackle cancer development and/or metastatic propension
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