Dsg2 increases exosome release and enhances EGFR/c-Src content: A mechanism for intercellular mitogenic effect

Authors

Andrew M. Overmiller, Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, *Genetics, Genomics, and Cancer Biology Graduate ProgramFollow
Jennifer A. Pierluissi, Department of Dermatology & Cutaneous Biology, Thomas Jefferson UniversityFollow
Peter J Wermuth, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Ubaldo E. Martinez-Outshoorn, MD, Thomas Jefferson UniversityFollow
Madalina Tuluc, Department of Pathology, Thomas Jefferson UniversityFollow
Adam J. Luginbuhl, Thomas Jefferson UniversityFollow
Joseph Curry, Thomas Jefferson UniversityFollow
Larry A. Harshyne, Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USAFollow
James K. Wahl, III, Department of Oral Biology, University of Nebraska, Lincoln, NE, USAFollow
Andrew P. South, Department of Dermatology & Cutaneous Biology, Thomas Jefferson UniversityFollow
M G Mahoney, Thomas Jefferson UniversityFollow

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Description

Abstract:

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.

Publication Date

4-13-2016

Keywords

Dsg2 increases exosome release and enhances EGFR/c-Src content: A mechanism for intercellular mitogenic effect, poster, Thomas Jefferson University

Disciplines

Dermatology

Comments

Presented at: 2016 Sigma XI; Student Research Day.

Recommended Citation

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.
https://jdc.jefferson.edu/dcbposters/1