Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.
Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma.
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DOI：
10.1038/sj.bjc.6604735
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发表时间：
2008-11-18
影响因子：
8.8
通讯作者：
Chen, Z. (G)
中科院分区：
文献类型：
--
作者：
Zhang, H.;Su, L.;Muller, S.;Tighiouart, M.;Xu, Z.;Zhang, X.;Shin, H. J. C.;Hunt, J.;Sun, S-Y;Shin, D. M.;Chen, Z. (G)
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还不清楚。与头颈部鳞状细胞癌（HNSCC）标本的原发肿瘤相比，在淋巴结转移中检测到Cav-1水平的显著降低（P<0.0001），证实了在源自我们的原位异种移植模型的高转移性M4细胞系中观察到的Cav-1下调。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显著低于EV肿瘤动物（P=0.03）。在体外，CavS细胞显示减少细胞生长，侵袭，并增加失巢凋亡与EV细胞相比。在CavS细胞中，Cav-1与整合素β1和Src形成复合物。将整合素β1中和抗体或Src抑制剂PP 2应用于EV细胞，显示出与CavS细胞相似的表型，提示Cav-1可能通过调节整合素β1和Src介导的细胞-细胞和细胞-基质相互作用而发挥抑制肿瘤发生和肺转移的作用。
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.
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影响因子：
11.2
作者：
Liu, Xiangguo;Yue, Ping;Sun, Shi-Yong
通讯作者：
Sun, Shi-Yong
影响因子：
3.9
作者：
Razani, B;Schlegel, A;Lisanti, MP
通讯作者：
Lisanti, MP
DOI：
10.1002/hed.20511
发表时间：
2007-03-01
影响因子：
2.9
作者：
Zhang, Xin;Hunt, Jennifer L.;Chen, Zhuo (Georgia)
通讯作者：
Chen, Zhuo (Georgia)
影响因子：
8
作者：
Sloan, EK;Stanley, KL;Anderson, RL
通讯作者：
Anderson, RL
影响因子：
6.2
作者：
Zhang, X;Liu, YN;Chen, Z
通讯作者：
Chen, Z