Role of Integrin β1 Metastasis of Head and Neck Squamous Cell Carcinoma
Purpose: This study aimed to understand the prognostic value of integrin b1 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 nonmetastatic primary tumors and 101 metastatic primary tumors were examined for the association of integrin b1 expression with metastasis and disease prognosis by appropriate statistical methods. Fluorescence-activated cell sorting was used to separate the integrin b1high/þ cell population from the integrin b1low/ population in HNSCC cell lines. These two populations and integrin b1 shRNA knockdown HNSCC cells were examined for the effect of integrin b1 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 b1 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 b1 expression was inversely correlated with overall survival (P ¼ 0.035). The integrin b1 knockdown or integrin b1low/ 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 b1 knockdown or integrin b1low/ HNSCC cells (P < 0.01). Finally, zymography results showed integrin b1- affected HNSCC invasion by regulating MMP-2 activation.
Conclusion: These findings indicate that integrin b1 has a major impact on HNSCC prognosis through its regulation of metastasis.
Wang D, Müller S, Amin AR, Huang D, Su L, Hu Z, Rahman MA, Nannapaneni S, Koenig L, Chen Z, Tighiouart M, Shin DM, Chen ZG. The pivotal role of integrin β1 in metastasis of head and neck squamous cell carcinoma. Clinical Cancer Research. 2012 Sep 1;18(17):4589-99. doi: 10.1158/1078-0432.CCR-11-3127.