Caveolin-1 tumor-promoting role in human melanoma.
Caveolin-1 (Cav-1), a member of the caveolin family, regulates caveolae-associated signaling proteins, which are involved in many biological processes, including cancer development. Cav-1 was found to exert a complex and ambiguous role as oncogene or tumor suppressor depending on the cellular microenvironment. Here we investigated Cav-1 expression and function in a panel of melanomas, finding its expression in all the cell lines. The exception was the primary vertical melanoma cell line, WM983A, characterized by the lack of Cav-1, and then utilized as a recipient for Cav-1 gene transduction to address a series of functional studies. The alleged yet controversial role of phospho (Ph)-Cav-1 on cell regulation was also tested by transducing the nonphosphorylatable Cav-1Y14A mutant. Wild-type Cav-1, but not mutated Cav-1Y14A, increased tumorigenicity as indicated by enhanced proliferation, migration, invasion and capacity of forming foci in semisolid medium. Accordingly, Cav-1 silencing inhibited melanoma cell growth reducing some of the typical traits of malignancy. Finally, we detected a secreted fraction of Cav-1 associated with cell released microvesicular particles able to stimulate in vitro anchorage independence, migration and invasion in a paracrine/autocrine fashion and, more important, competent to convey metastatic asset from the donor melanoma to the less aggressive recipient cell line. A direct correlation between Cav-1 levels, the amount of microvesicles released in the culture medium and MMP-9 expression was also observed.
Felicetti
Federica
F
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy.
Parolini
Isabella
I
Bottero
Lisabianca
L
Fecchi
Katia
K
Errico
Maria Cristina
MC
Raggi
Carla
C
Biffoni
Mauro
M
Spadaro
Francesca
F
Lisanti
Michael P
MP
Sargiacomo
Massimo
M
Carè
Alessandra
A
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9