Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.
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.
Zhang
H
H
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
Su
L
L
Müller
S
S
Tighiouart
M
M
Xu
Z
Z
Zhang
X
X
Shin
H J C
HJ
Hunt
J
J
Sun
S-Y
SY
Shin
D M
DM
Chen
Z G
ZG
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
D051242:Caveolin 1