| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lupia, Antonella Peppicelli, Silvia Witort, Ewa Bianchini, Francesca Carloni, Vinicio Pimpinelli, Nicola Urso, Carmelo Borgognoni, Lorenzo Capaccioli, Sergio Calorini, Lido Lulli, Matteo |
| Description |
Country affiliation: Italy Author Affiliation: Lupia A ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Peppicelli S ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Witort E ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Bianchini F ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Carloni V ( Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.); Pimpinelli N ( Clinical, Preventive and Oncologic Dermatology Section, Department Critical Care Medicine and Surgery, University of Florence, Florence, Italy.); Urso C ( Department of Anatomic Pathology, Santa Maria Annunziata Hospital, Florence, Italy.); Borgognoni L ( Plastic Surgery Unit, Regional Melanoma Referral Center, Tuscan Tumor Institute (ITT), Santa Maria Annunziata Hospital, Florence, Italy.); Capaccioli S ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Calorini L ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.); Lulli M ( Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.) |
| 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 TGFß. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma. |
| File Format |
HTM / HTML |
| ISSN |
0022202X |
| e-ISSN |
15231747 |
| Journal |
Journal of Investigative Dermatology |
| Issue Number |
12 |
| Volume Number |
134 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Dermatology Antigens, Cd63 Physiology Disease Progression Epithelial-mesenchymal Transition Melanoma Physiopathology Skin Neoplasms Animals Drug Effects Genetics Cadherins Cell Line, Tumor Cell Movement Disease Models, Animal Gene Silencing Heterografts Pathology Mice Mice, Scid Rna, Small Interfering Pharmacology Transcription Factors Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology Dermatology |
