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Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes
Author(s) -
Overmiller Andrew M.,
Pierluissi Jennifer A.,
Wermuth Peter J.,
Sauma Sami,
MartinezOutschoorn Ubaldo,
Tuluc Madalina,
Luginbuhl Adam,
Curry Joseph,
Harshyne Larry A.,
Wahl James K.,
South Andrew P.,
Mahoney Mỹ G.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601138rr
Subject(s) - exosome , desmoglein , cadherin , extracellular vesicle , cancer research , tumor microenvironment , microbiology and biotechnology , chemistry , microvesicles , cancer , cell , biology , medicine , microrna , biochemistry , gene
ABSTRACT Extracellular vesicles (EVs) are nanoscale membrane‐derived vesicles that serve as intercellular messengers carrying lipids, proteins, and genetic material. Substantial evidence has shown that cancer‐derived EVs, secreted by tumor cells into the blood and other bodily fluids, play a critical role in modulating the tumor microenvironment and affecting the pathogenesis of cancer. Here we demonstrate for the first time that squamous cell carcinoma (SCC) EVs were enriched with the C‐terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in malignancies. Overexpression of Dsg2 increased EV release and mitogenic + fibroblasts. Furthermore, SCC EVs activated Erk1/2 and Akt signaling and enhanced fibroblast cell proliferation. In vivo, Dsg2 was highly up‐regulated in the head and neck SCCs, and EVs isolated from sera of patients with SCC were enriched in Dsg2 C‐terminal fragment and epidermal growth factor receptor. This study defines a mechanism by which Dsg2 expression in cancer cells can modulate the tumor microenvironment, a step critical for tumor progression.—Overmiller, A. M., Pierluissi, J. A., Wermuth, P. J., Sauma, S., Martinez‐Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L. A., Wahl, J. K. III, South, A. P., Mahoney, M. G. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes. FASEB J . 31, 3412–3424 (2017). www.fasebj.org