title: CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.
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.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Lupia
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Peppicelli
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Ewa
authors.initials: E
authors.lastname: Witort
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Carloni
authors.affiliation: Clinical, Preventive and Oncologic Dermatology Section, Department Critical Care Medicine and Surgery, University of Florence, Florence, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pimpinelli
authors.affiliation: Department of Anatomic Pathology, Santa Maria Annunziata Hospital, Florence, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Urso
authors.affiliation: Plastic Surgery Unit, Regional Melanoma Referral Center, Tuscan Tumor Institute (ITT), Santa Maria Annunziata Hospital, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Borgognoni
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Capaccioli
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. Electronic address: lido.calorini@unifi.it.
authors.forename: Lido
authors.initials: L
authors.lastname: Calorini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. Electronic address: matteo.lulli@unifi.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lulli
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D000071250:Snail Family Transcription Factors; D060149:Tetraspanin 30 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: C554586:CD63 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D060149:Tetraspanin 30; D014157:Transcription Factors