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Exosomes are nanoscale membrane-derived vesicles that are secreted by cancer cells and play a critical role in modulating the tumor microenvironment and disease pathogenesis. Dsg2, a desmosomal cadherin often overexpressed in skin malignancies including squamous cell carcinoma (SCC), can activate EGFR/c-Src signaling and promote oncogenesis. We sought to address the potential role of Dsg2 in exosome biogenesis and intercellular signaling in SCC. Here, purified exosomes from SCC cells and head/neck SCC patient sera were enriched with a processed 65 kDa membrane-associated C-terminal fragment of Dsg2. Cells overexpressing Dsg2 had increased exosome release and protein content and produced particles enriched with EGFR/c-Src, enhancing proliferation in recipient fibroblasts, compared to parental cell exosomes. This study suggests a mechanism by which SCC cells can promote intercellular signaling and modulate the tumor microenvironment through enhanced Dsg2 levels.
Dsg2 increases exosome release and enhances EGFR/c-Src content: A mechanism for intercellular mitogenic effect, poster, Thomas Jefferson University
Overmiller, Andrew M.; Pierluissi, Jennifer A.; Wermuth, Peter J; Martinez-Outshoorn, MD, Ubaldo E.; Tuluc, Madalina; Luginbuhl, Adam J.; Curry, Joseph; Harshyne, Larry A.; Wahl, III, James K.; South, Andrew P.; and Mahoney, M G, "Dsg2 increases exosome release and enhances EGFR/c-Src content: A mechanism for intercellular mitogenic effect" (2016). Department of Dermatology and Cutaneous Biology Posters. 1.