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CD63 Tetraspanin Is a Negative Driver of Epithelial-to-Mesenchymal Transition in Human Melanoma Cells

Authors :
Francesca Bianchini
Lorenzo Borgognoni
Lido Calorini
Matteo Lulli
Antonella Lupia
Vinicio Carloni
Nicola Pimpinelli
Ewa Witort
Carmelo Urso
Sergio Capaccioli
Silvia Peppicelli
Source :
Journal of Investigative Dermatology. 134:2947-2956
Publication Year :
2014
Publisher :
Elsevier BV, 2014.

Abstract

The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

Details

ISSN :
0022202X
Volume :
134
Database :
OpenAIRE
Journal :
Journal of Investigative Dermatology
Accession number :
edsair.doi.dedup.....b3caae1b1ac2ef3bc9f608343fe7460a
Full Text :
https://doi.org/10.1038/jid.2014.258