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首页> 美国卫生研究院文献>British Journal of Cancer >Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma
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Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma

机译：Caveolin-1表达的恢复抑制头颈部鳞状细胞癌的生长和转移

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摘要

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 β1 and Src. Further application of integrin β1 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 β1- and Src-mediated cell–cell and cell–matrix interactions.
机译：Caveolin-1（Cav-1）在调节细胞信号传导中起重要作用，但其在转移中的作用尚未明确。与头颈部鳞状细胞癌（HNSCC）标本相比，淋巴结转移中Cav-1水平显着降低（P <0.0001），证实了在高度转移性M4细胞中Cav-1的下调。来源于我们原位异种移植模型的细胞系。为了研究Cav-1在HNSCC转移中的功能，我们在体外和原位异种移植模型中比较了携带人cav-1 cDNA（CavS）的M4细胞与表达空载体（EV）的细胞的稳定克隆。与EV肿瘤相比，Cav-1的过表达抑制了CavS肿瘤的生长。携带CavS肿瘤的动物的肺转移发生率明显低于携带EV肿瘤的动物（P = 0.03）。在体外，与EV细胞相比，CavS细胞显示出减少的细胞生长，侵袭和增加的神经缺损。在CavS细胞中，Cav-1与整联蛋白β1和Src形成复合物。整合素β1中和抗体或Src抑制剂PP2在EV细胞上的进一步应用显示了与CavS细胞相似的表型，这表明Cav-1可能通过调节整合素β1-和Src介导的细胞和细胞在肿瘤发生和肺转移中发挥抑制作用。 –矩阵交互。

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