title: Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.
abstract: Caveolin-1 (Cav-1) plays an important role in modulating cellular signalling, but its role in metastasis is not well defined. A significant reduction in Cav-1 levels was detected in lymph node metastases as compared with primary tumour of head and neck squamous cell carcinoma (HNSCC) specimens (P<0.0001), confirming the downregulation of Cav-1 observed in a highly metastatic M4 cell lines derived from our orthotopic xenograft model. To investigate the function of Cav-1 in metastasis of HNSCC, we compared stable clones of M4 cells carrying human cav-1 cDNA (CavS) with cells expressing an empty vector (EV) in vitro and in the orthotopic xenograft model. Overexpression of Cav-1 suppressed growth of the CavS tumours compared with the EV tumours. The incidence of lung metastases was significantly lower in animals carrying CavS tumours than those with EV tumours (P=0.03). In vitro, CavS cells displayed reduced cell growth, invasion, and increased anoikis compared with EV cells. In CavS cells, Cav-1 formed complex with integrin beta1 and Src. Further application of integrin beta1 neutralising antibody or Src inhibitor PP2 to EV cells illustrated similar phenotypes as CavS cells, suggesting that Cav-1 may play an inhibitory role in tumorigenesis and lung metastasis through regulating integrin beta1- and Src-mediated cell-cell and cell-matrix interactions.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Su
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Tighiouart
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: H J C
authors.initials: HJ
authors.lastname: Shin
authors.forename: J
authors.initials: J
authors.lastname: Hunt
authors.forename: S-Y
authors.initials: SY
authors.lastname: Sun
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: Z G
authors.initials: ZG
authors.lastname: Chen
mesh_terms: D000818:Animals; D023102:Anoikis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000503:physiopathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000503:physiopathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D023041:Xenograft Model Antitumor Assays
chemical_list: D051242:Caveolin 1