Department of Translational Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Int J Oncol. 2013 Nov;43(5):1523-30. doi: 10.3892/ijo.2013.2097. Epub 2013 Sep 13.
Esophageal squamous cell carcinoma (ESCC), the most common subtype of esophageal cancer in East Asian countries, is a devastating disease characterized by distinctly high incidence and mortality rates. Our previous expression profile analysis showed that integrin alpha 6 (ITGA6) is highly expressed in ESCC tissues. To validate cell surface expression of ITGA6 as a novel target in ESCC, we investigated ITGA6 expression in tumor tissue samples and cell lines of ESCC and found that ITGA6 was upregulated in these cells. In vitro knockdown of ITGA6 in ESCC cells resulted in inhibition of cell proliferation, invasion and colony formation. In addition, we demonstrated that ITGA6 associates with integrin beta 4 (ITGB4), and that this heterodimer complex is upregulated in both ESCC tissues and cell lines. Moreover, our biodistribution results in an ESCC xenograft model indicated that ITGA6 is a possible target for antibody-related diagnostic and therapeutic modalities in ESCC. Thus, our findings suggest that ITGA6 plays an important role in tumorigenesis in ESCC and represents a potential therapeutic target in the treatment of ESCC.
食管鳞状细胞癌（ESCC）是东亚国家最常见的食管癌亚型，是一种破坏性疾病，其发病率和死亡率明显较高。我们之前的表达谱分析表明，整合素 alpha 6（ITGA6）在 ESCC 组织中高度表达。为了验证 ITGA6 作为 ESCC 新靶标的细胞表面表达，我们研究了 ESCC 肿瘤组织样本和细胞系中的 ITGA6 表达，发现这些细胞中 ITGA6 上调。在 ESCC 细胞中体外敲低 ITGA6 导致细胞增殖、侵袭和集落形成受到抑制。此外，我们证明 ITGA6 与整合素 beta 4（ITGB4）结合，这种异二聚体复合物在 ESCC 组织和细胞系中均上调。此外，我们在 ESCC 异种移植模型中的生物分布结果表明，ITGA6 可能是 ESCC 抗体相关诊断和治疗方法的潜在靶标。因此，我们的研究结果表明，ITGA6 在 ESCC 的肿瘤发生中起重要作用，是 ESCC 治疗的潜在治疗靶点。
