Twist1 Is Up-Regulated in Gastric Cancer-Associated Fibroblasts with Poor Clinical Outcomes
Twist1 Is Up-Regulated in Gastric Cancer-Associated Fibroblasts with Poor Clinical Outcomes
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DOI：
10.1016/j.ajpath.2011.06.032
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发表时间：
2011-10-01
影响因子：
6
通讯作者：
Kim, Seok-Hyung
中科院分区：
文献类型：
--
作者：
Sung, Chang Ohk;Lee, Keun-Woo;Kim, Seok-Hyung
间质成纤维细胞在癌症的发生和发展中起着重要作用。Twist1是一种基本的螺旋-环-螺旋转录因子，其过表达通常与许多肿瘤的侵袭性行为有关。在本研究中，我们在验证了四种商用Twist1特异性抗体的有效性后，使用单克隆Twist1抗体研究了Twist1在胃间质成纤维细胞和癌细胞中的表达模式。Twist1的表达在胃癌相关成纤维细胞（CAFs）中比在其他癌细胞中更常见，但在非癌组织中很少表达。在激光捕获间质成纤维细胞显微解剖中，Tvvist1免疫阳性成纤维细胞表现出显著增加的Twist1、成纤维细胞特异性蛋白1和CXCL14 mRNA表达。此外，Twist1 mRNA的表达与血小板衍生生长因子受体13和a的表达呈显著的线性相关。我们发现，来自表达Twist1的皮肤和肺成纤维细胞的条件培养基显著促进胃癌细胞的体外侵袭。在195例胃癌样本中，CAF Twist1的表达与肿瘤大小、浸润深度和淋巴结转移有关。Twist1也与胃癌患者的不良预后相关，尤其是弥漫性胃癌患者。综上所述，胃癌的cas经常改变Twist1的表达，而成纤维细胞中Twist1表达的增加有助于癌细胞的进展和患者的生存率降低。（中国病理杂志，2011,170:1827-1838;DOI: 10.1016/ j.j ajpath.2011.06.032）
Stromal fibroblasts perform important roles in cancer development and progression. Overexpression of Twist1, a basic helix-loop-helix transcription factor, is often associated with aggressive behavior in many tumors. In this study, we investigated Twist1 expression patterns in gastric stromal fibroblasts and cancer cells using a monoclonal Twist1 antibody after validating the effectiveness of four commercial Twist1-specific antibodies. Twist1 expression was more frequently observed in gastric cancer-associated fibroblasts (CAFs) than in other cancer cells but was otherwise rarely expressed in noncancerous tissue. In laser capture microdissection of stromal fibroblasts, Tvvist1 immunopositive fibroblasts exhibited significantly increased Twist1, fibroblast-specific protein 1, and CXCL14 mRNA expression. Furthermore, Twist1 mRNA expression showed a significant linear correlation with that of platelet-derived growth factor receptors 13 and a. We found that conditioned media from Twist1-expressing skin and lung fibroblasts significantly promote invasion of gastric cancer cells in vitro. In 195 gastric cancer samples, CAF Twist1 expression was associated with tumor size, invasion depth, and lymph node metastasis. Twist1 was also associated with poor prognosis in patients with gastric cancer, particularly in those with the diffuse type. In conclusion, CAFs in gastric cancer frequently have altered Twist1 expression, and increased Twist1 expression in fibroblasts contributes to the progression of cancer cells and poor patient survival. (Am J Pathol 2011, 170:1827-1838; DOI: 10.1016/j.ajpath.2011.06.032)