Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer.
Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer.
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发表时间：
2000-11
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通讯作者：
Y. Yonemura;Y. Endou;K. Kimura;S. Fushida;E. Bandou;K. Taniguchi;K. Kinoshita;I. Ninomiya;K. Sugiyama;C. Heizmann;B. Schafer;Takuma Sasaki
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作者：
Y. Yonemura;Y. Endou;K. Kimura;S. Fushida;E. Bandou;K. Taniguchi;K. Kinoshita;I. Ninomiya;K. Sugiyama;C. Heizmann;B. Schafer;Takuma Sasaki
已知S100A4通过其激活非肌肉肌球蛋白的能力参与癌细胞运动。E-钙粘蛋白在嗜同性细胞间粘附中起重要作用，被称为侵袭抑制基因。本研究从E-cadherin和S100A4表达的相互关系方面探讨胃癌的组织学类型和转移潜能。采用逆转录-PCR、Western blot和免疫组化方法检测E-cadherin和S100A4在胃癌细胞系、原发性胃癌和正常对照中的表达。S100A4蛋白和E-cadherin在8株胃癌细胞系中有5株表达，在4株胃癌细胞系中呈反向表达。在临床标本中，分化腺癌中E-cadherin mRNA的表达率（88%，14/16）显著高于低分化腺癌（50%，22/44; P = 0.015）。Western blot分析表明，低分化腺癌中S100A4蛋白的表达是高分化腺癌的1.6倍。免疫组化结果显示，在92例原发性胃癌中，51例（55%）表达S100A4。在92例原发性肿瘤中，66例（72%）发现E-cadherin表达降低。S100 A4在低分化腺癌中的表达与淋巴结转移或腹膜转移密切相关。E-cadherin表达减少与阳性浆膜受累和浸润型密切相关。E-cadherin减少和S100A4高表达的肿瘤表现为腹膜播散、浆膜浸润和浸润性生长。此外，这些肿瘤与低分化腺癌有很强的相关性。相反，E-cadherin保留和S100A4低表达的肿瘤与高分化腺癌关系密切，预后良好。通过考克斯比例风险模型，S100 A4和E-cadherin组织状态被判断为独立的预后因素。S100A4和E-cadherin组织状态可能是评估胃癌转移潜能和预后的有力辅助手段。
S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate nonmuscle myosin. E-cadherin has an important role in the homophilic cell-cell adhesion and is called an invasion suppressor gene. In the current study, we investigate the histological type and metastatic potential of gastric cancer from the aspect of the interrelationship of E-cadherin and S100A4 expression. Expression of E-cadherin and S100A4 in gastric cancer cell lines, primary gastric cancers, and their normal counterparts were analyzed by reverse transcription-PCR, Western blot, and immunohistochemical methods. S100A4 protein and E-cadherin were expressed in five of eight gastric cancer cell lines, and inverse expression of the two proteins are found in four cell lines. In the clinical specimens, E-cadherin mRNA expression in differentiated adenocarcinomas (88%, 14 of 16) was significantly more frequent than that in poorly differentiated adenocarcinomas (50%, 22 of 44; P = 0.015). Western blot analysis demonstrates that S100A4 protein expression in poorly differentiated adenocarcinomas was 1.6-fold higher than in well differentiated adenocarcinoma. Immunohistochemically, S100A4 expression was detected in 51 (55%) of 92 primary gastric cancers. Reduced expression of E-cadherin in primary tumors was found in 66 (72%) of 92 tumors. S100A4 expression in the poorly differentiated adenocarcinomas had a strong relation to positive lymph node involvement or peritoneal dissemination. Reduced E-cadherin expression showed a strong relationship with positive serosal involvement and infiltrating type. Tumors classified as a group with reduced E-cadherin and high expression of S100A4 reveal positive peritoneal dissemination, serosal involvement, and infiltrating type in the growth pattern. Furthermore, these tumors showed a strong correlation with the poorly differentiated adenocarcinoma. In contrast, tumors with preserved E-cadherin and low expression of S100A4 have a close relation to the well differentiated adenocarcinoma and a favorable prognosis. By the Cox proportional hazard model, S100A4 and E-cadherin tissue status was judged as an independent prognostic factor. S100A4 and E-cadherin tissue status may be a powerful aid in evaluating metastatic potential or the prognosis of patients with gastric cancer.