Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma.
Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma.
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发表时间：
2011-03
影响因子：
2
通讯作者：
Y. Nagai;Masayuki Watanabe;S. Ishikawa;R. Karashima;J. Kurashige;S. Iwagami;M. Iwatsuki;Y. Baba;Y. Imamura;N. Hayashi;H. Baba
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作者：
Y. Nagai;Masayuki Watanabe;S. Ishikawa;R. Karashima;J. Kurashige;S. Iwagami;M. Iwatsuki;Y. Baba;Y. Imamura;N. Hayashi;H. Baba
背景/目的Wingless/int-1（Wnt）诱导的分泌蛋白-1（WISP-1/CCN 4）是Cyr 61-CTGF-Nov（CCN）家族的成员，在多种肿瘤中的表达已被检测。然而，WISP-1的表达与食管鳞状细胞癌（ESCC）的临床特征之间的关系仍有待阐明。本研究旨在明确WISP-1蛋白在食管癌患者中的表达，并在体外研究WISP-1在食管癌细胞中的功能。患者和方法190例胸段食管癌患者在2005年至2009年间接受了经胸食管次全切除术。排除所有接受过既往治疗的患者，并使用WISP-1抗体对190份ESCC样本中的105份进行化学分析。RT-PCR检测食管癌细胞系中WISP-1 mRNA的表达。使用WISP-1转染的细胞进行生长测定和侵袭测定。结果免疫组化分析显示WISP-1阳性表达与肿瘤大小、肿瘤类型、淋巴结转移及预后不良密切相关。浸润型肿瘤中WISP-1阳性表达明显多于扩张型肿瘤。在检测的食管癌细胞系中，仅TE 8表达WISP-1 mRNA。与对照细胞相比，WISP-1转染细胞的生长显著增加，但在转染细胞和对照细胞之间没有观察到侵袭活性的差异。结论WISP-1的表达可能在食管鳞癌的发生发展中起重要作用。因此，WISP-1可能是ESCC患者预后不良的临床标志物，也可能是控制ESCC进展的治疗靶点。
BACKGROUND/AIM The expression of Wingless/int-1 (Wnt)-induced secreted protein-1 (WISP-1/CCN4), a member of the Cyr61-CTGF-Nov (CCN) family, has been examined in several types of cancer. However, the correlation between the WISP-1 expression and the clinical features of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. This study aimed to clarify the expression of WISP-1 protein in patients with ESCC and also to examine the function of WISP-1 in esophageal cancer cells in vitro. PATIENTS AND METHODS One-hundred and ninety patients with thoracic esophageal carcinoma underwent transthoracic subtotal esophagectomy-between 2005 and 2009. All patients that had received previous therapy were excluded and 105 out of the 190 ESCC samples were analyzed immunohistochemically using WISP-1 antibody. The expression of WISP-1 mRNA in esophageal cancer cell lines was analyzed by RT-PCR. Growth assay and invasion assays were performed using WISP-1 transfected cells. RESULTS The immunohistochemical analysis showed that WISP-1-positive cases were closely associated with tumor size, tumor type, lymph node metastasis and poor prognosis. There were significantly more WISP-1-positive infiltrative type tumors than expanding type tumors. In the esophageal cancer cell lines examined, only TE8 expressed WISP-1 mRNA. The growth of WISP-1-transfected cells was significantly increased in comparison to the control cells, but no differences in the invasion activity were observed between the transfected cells and control cells. CONCLUSION The expression of WISP-1 may play an important role in the progression of ESCC. WISP-1 could therefore be a clinical marker for a poor prognosis in patients with ESCC and may also be a therapeutic target to control the progression of ESCC.