N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma
N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma
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DOI：
10.1158/1078-0432.ccr-0578-03
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发表时间：
2004-06-15
影响因子：
11.5
通讯作者：
Imamura, M
中科院分区：
文献类型：
--
作者：
Nakajima, S;Doi, R;Imamura, M
目的：细胞间粘附的丧失和细胞运动的增加促进肿瘤细胞的侵袭。在本研究中，E-和N-钙粘蛋白，经典的钙粘蛋白家族的成员，被调查作为诱导上皮间质转化（EMT），被认为是发挥了根本性的作用，在早期步骤的侵袭和转移的癌症。已知细胞生长因子调节细胞粘附分子。本研究的目的是探讨是否在胰腺癌的N-钙粘蛋白的增益是通过EMT和是否其表达的转移过程中所涉及的生长factors.Experimental设计：我们化学检测的N-和E-钙粘蛋白和波形蛋白，间充质标志物，在胰腺原发性和转移性肿瘤的表达。N-钙粘蛋白，转化生长因子（TGF）β，和成纤维细胞生长因子2的表达之间的相关性进行了评价，在培养的细胞系中，生长因子的钙粘蛋白和波形蛋白的诱导进行了检查。N-cadherin表达与神经浸润（P = 0.008）、组织学类型（P = 0.043）、原发肿瘤中成纤维细胞生长因子表达（P = 0.007）、转移肿瘤中TGF表达（P = 0.004）和波形蛋白表达（P = 0.01）相关。波形蛋白是一种间充质标志物，在原发性肿瘤的少数癌细胞中观察到，但在肝转移中大量表达。结论：本研究为胰腺癌EMT的发生提供了形态学依据，揭示了N-cadherin的过度表达参与了胰腺癌EMT的发生，并受到生长因子的影响。
Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors.Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)beta, and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines.Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change.Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.