Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Oncol Rep. 2013 Apr;29(4):1570-8. doi: 10.3892/or.2013.2273. Epub 2013 Feb 5.
CD44 standard isoform (CD44s) is a cancer stem cell marker in many tumors, and is one of the CD44 isoforms.CD44v6 has been reported to correlate with tumor progression and poor prognosis in colorectal cancer. However, the relevance of CD44s and CD44v6 to epithelial-mesenchymal transition (EMT) remains unclear. Immunohistochemistry was performed to investigate the clinical importance of CD44s and CD44v6 and their relevance to EMT in 113 patients with stage II/III colorectal cancer treated by curative resection. The relevance of CD44v6 knockdown to the phenotype of colon cancer cells was examined using small interfering RNA (siRNA) specific for CD44v6 in vitro. CD44v6 expression showed a significant inverse correlation with E-cadherin expression (P=0.0007) and a positive correlation with vimentin expression (P=0.0096). A multivariate analysis showed that high CD44v6 expression was an independent poor prognostic factor for disease-free survival (P=0.01, HR=3.05) and overall survival (P=0.025, HR=3.16). The clinical significance and the relevance of CD44s expression to EMT markers was noted to a lesser extent compared to CD44v6 expression. The knockdown of CD44v6 decreased vimentin expression, cell invasion and HGF-induced cell migration, but conferred only a slight effect on E-cadherin expression in colon cancer cells (HCT116 and LoVo). CD44v6 is related to poor outcome of patients with colorectal cancer via upregulation of the mesenchymal phenotype.
CD44 标准同工型（CD44s）是许多肿瘤中的癌症干细胞标志物，也是 CD44 同工型之一。已有报道称，CD44v6 与结直肠癌的肿瘤进展和预后不良相关。然而，CD44s 和 CD44v6 与上皮-间充质转化（EMT）的相关性尚不清楚。本研究通过免疫组织化学方法，检测了 113 例接受根治性切除术治疗的 II/III 期结直肠癌患者中 CD44s 和 CD44v6 的临床意义及其与 EMT 的相关性。采用针对 CD44v6 的小干扰 RNA（siRNA），在体外检测 CD44v6 敲低对结肠癌细胞表型的相关性。CD44v6 的表达与 E-钙黏蛋白的表达呈显著负相关（P=0.0007），与波形蛋白的表达呈正相关（P=0.0096）。多因素分析显示，高 CD44v6 表达是无病生存（P=0.01，HR=3.05）和总生存（P=0.025，HR=3.16）的独立不良预后因素。与 CD44v6 表达相比，CD44s 表达的临床意义和与 EMT 标志物的相关性较小。CD44v6 的敲低降低了波形蛋白的表达、细胞侵袭和 HGF 诱导的细胞迁移，但对结肠癌细胞（HCT116 和 LoVo）中 E-钙黏蛋白的表达仅产生轻微影响。CD44v6 通过上调间充质表型与结直肠癌患者的不良预后相关。
