Extracellular Vesicles in Cancer ProgressionMonday, 17 February 2020 at 15:00  Add to Calendar ▼2020-02-17 18:00:002020-02-17 19:00:00Europe/LondonExtracellular Vesicles in Cancer ProgressionEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.comA variety of studies has shown the role of cancer cell-derived extracellular vesicles (EVs) in tumor progression. Our and others’ studies have also demonstrated that cancer cell-derived small EVs (sEVs) target multiple recipient cells, such as cancer cells as well as monocytes in the tumor microenvironment (TME). We have specifically shown that prostate cancer cell-derived sEVs are taken up by cancer cells and monocytes and they are equally efficient in modulating the functions of these cells. This is expected since tumor growth is supported by all components of the TME and requires monocyte differentiation into a M2 pro-tumorigenic phenotype. We now demonstrate that the alphaV integrins are up-regulated in circulating prostate cancer sEVs, and play a major role in the sEV functions described above. We demonstrate that de novo alphaV integrins’ expression in TME cells is not caused by increased mRNA levels but rather by sEV-mediated protein transfer. We have used CRISPR-Cas9 technology and current approaches recommended by MISEV2018 to isolate sEVs lacking alphaVbeta3 or alphaVbeta6 integrins. We specifically show that in vivo and in vitro sEVs containing these integrins are required to reprogram cancer cells toward a very aggressive neuroendocrine phenotype, or to increase pro-angiogenic activities of microvascular endothelium. The ability of the alphaVbeta3 and alphaVbeta6 integrins to affect a specific target cell via sEVs appears to be mediated by their unique beta subunit and by activation of specific signaling pathways. Overall, our recent investigations show that the expression of the alphaV integrins in sEVs generates vesicles that have pro-tumorigenic activities. Thus, we conclude that inhibition of these integrins and their downstream effectors might offer novel therapeutic strategies in prostate cancer. We also conclude that alphaV integrins in prostate cancer patient sEVs may be a clinically useful and non-invasive biomarker for prostate cancer progression. |
Add to Calendar ▼2020-02-17 00:00:002020-02-18 00:00:00Europe/LondonEV-based Diagnostics, Delivery and TherapeuticsEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
