title: The pivotal role of integrin β1 in metastasis of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  This study aimed to understand the prognostic value of integrin β1 expression in head and neck squamous cell carcinoma (HNSCC) and the mechanism underlying its association with metastatic HNSCC.
  
  
  METHODS
  Archival HNSCC tissues including 99 nonmetastatic primary tumors and 101 metastatic primary tumors were examined for the association of integrin β1 expression with metastasis and disease prognosis by appropriate statistical methods. Fluorescence-activated cell sorting was used to separate the integrin β1(high/+) cell population from the integrin β1(low/-) population in HNSCC cell lines. These two populations and integrin β1 shRNA knockdown HNSCC cells were examined for the effect of integrin β1 on invasion in vitro and on lymph node and lung metastases in a xenograft mouse model. Expression and activation of matrix metalloproteinases (MMP) were examined by zymography.
  
  
  RESULTS
  Statistical analysis showed that integrin β1 expression was significantly higher in the metastatic primary tumors than in the nonmetastatic tumors (42.6% vs. 24.8%, P < 0.0001 and P < 0.0001 by univariate and multivariate analyses, respectively). In patients with lymph node metastasis, integrin β1 expression was inversely correlated with overall survival (P = 0.035). The integrin β1 knockdown or integrin β1(low/-) HNSCC cells showed a significant reduction in lymph node and lung metastases in vivo (P < 0.001 and P < 0.05, respectively). Significantly reduced Matrigel invasion capability was also found in integrin β1 knockdown or integrin β1(low/-) HNSCC cells (P < 0.01). Finally, zymography results showed integrin β1-affected HNSCC invasion by regulating MMP-2 activation.
  
  
  CONCLUSIONS
  These findings indicate that integrin β1 has a major impact on HNSCC prognosis through its regulation of metastasis.
authors: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Road, Suite C3086, Atlanta, GA 30322, USA.
authors: Dongsheng
authors: D
authors: Wang
authors: Susan
authors: S
authors: Müller
authors: A R M Ruhul
authors: AR
authors: Amin
authors: Donghai
authors: D
authors: Huang
authors: Ling
authors: L
authors: Su
authors: Zhongliang
authors: Z
authors: Hu
authors: Mohammad Aminur
authors: MA
authors: Rahman
authors: Sreenivas
authors: S
authors: Nannapaneni
authors: Lydia
authors: L
authors: Koenig
authors: Zhengjia
authors: Z
authors: Chen
authors: Mourad
authors: M
authors: Tighiouart
authors: Dong M
authors: DM
authors: Shin
authors: Zhuo G
authors: ZG
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D034741:RNA, Small Interfering; D014183:Transplantation, Heterologous
chemical_list: D019012:Integrin beta1; D034741:RNA, Small Interfering