期刊
BRITISH JOURNAL OF CANCER
卷 99, 期 10, 页码 1684-1694出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6604735
关键词
squamous cell carcinoma of the head and neck; caveolin-1; integrin beta 1; Src
类别
资金
- National Institutes of Health [R21 DE014767]
- Georgia Cancer Coalition Distinguished Scholar
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 beta 1 and Src. Further application of integrin beta 1 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 beta 1- and Src-mediated cell-cell and cell-matrix interactions.
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