The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma

• Type of Material: Article
• Authors: Dongsheng Wang, Emory University; Susan Muller, Emory University; A R M Ruhul Amin, Emory University; Donghai Huang, Emory University; Ling Su, Emory University; Zhongliang Hu, Emory University; Mohammad Aminur Rahman, Emory University; Sreenivas Nannapaneni, Emory University; Lydia Koenig, Emory University; Zhengjia Chen, Emory University; Mourad Tighiouart, Emory University; Dong M Shin, Emory University; Zhuo G. Chen, Emory University
• Language: English
• Date: 2012-09-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012, American Association for Cancer Research
• Final Published Version (URL): http://clincancerres.aacrjournals.org/content/18/17/4589.long
• Title of Journal or Parent Work: Clinical Cancer Research
• ISSN: 1078-0432
• Volume: 18
• Issue: 17
• Start Page: 4589
• End Page: 4599
• Grant/Funding Information: This study was supported by a GCC Distinguished Scholar Award and NIH/NCI R21 CA125062 to Z(G)C.
• Research Categories: Biology, Bioinformatics; Health Sciences, Pathology; Health Sciences, Oncology

Abstract

Purpose 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. Experimental Design Archival HNSCC tissues including 99 non-metastatic 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 β1high/+ cell population from the integrin β1low/− population in HNSCC cell lines. These two populations and integrin β1 shRNA knock-down 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 (MMPs) were examined by zymography. Results Statistical analysis showed that integrin β1 expression was significantly higher in the metastatic primary tumors than in the non-metastatic 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 knock-down or integrin β1low/− 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 knock-down or integrin β1low/− HNSCC cells (p< 0.01). Finally, zymography results showed integrin β1 affected HNSCC invasion by regulating MMP-2 activation. Conclusion These findings indicate that integrin β1 has a major impact on HNSCC prognosis through its regulation of metastasis.