Abstract

Extracellular Vesicle Integrins: Novel Opportunities for the Diagnosis and Therapy of Cancer

Lucia R. Languino, Professor of Cancer Biology, Thomas Jefferson University

The benefits of cancer therapy mediated by small extracellular vesicles (sEVs) are: low immunogenicity, ability to infiltrate biological barriers and ‘targetability’.  Cancer cells cross-talk with the tumor microenvironment by releasing sEVs.  Our studies have revealed a role for integrins in sEVs in mediating cancer cell cross-talk with the tumor microenvironment.  After confirming the fidelity of the sEV preparations by electron microscopy, density gradient, and immunoblotting, we have determined that integrins are actively packaged into sEVs isolated from cancer cells.  sEVs mediate protein transfer of integrins to microvascular endothelial cells and increase the number of their junctions and tubules.  We have also demonstrated a cross-talk between prostate cancer cells and monocytes that affects macrophage functions and have suggested that inhibition of integrins might offer a novel immune–based therapeutic strategy in prostate cancer.  Overall, these studies show that sEVs from cancer cells may contribute to a horizontal propagation of integrin-associated phenotypes from cancer cells to the tumor microenvironment. We finally demonstrate that the sEVs circulating in plasma from prostate cancer patients contain higher levels of specific integrins, as compared to plasma sEVs from age-matched healthy subjects.  Our results suggest that specific integrins in cancer patient sEVs could be clinically useful as non-invasive biomarkers for cancer progression.