Xu Wen, Hu Xinlei, Chen Zhongting, Zheng Xiaoping, Zhang Chenjing, Wang Gang, Chen Yu, Zhou Xinglu, Tang Xiaoxiao, Luo Laisheng, Xu Xiang, Pan Wensheng
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Department of Orthopedics, Second Affiliated Hospital (Binjiang Branch) of Zhejiang University, School of Medicine, Hangzhou, China.
PLoS One. 2014 May 20;9(5):e97306. doi: 10.1371/journal.pone.0097306. eCollection 2014.
A tumor is considered a heterogeneous complex in a three-dimensional environment that is flush with pathophysiological and biomechanical signals. Cell-stroma interactions guide the development and generation of tumors. Here, we evaluate the contributions of normal fibroblasts to gastric cancer.
METHODOLOGY/PRINCIPAL FINDINGS: By coculturing normal fibroblasts in monolayers of BGC-823 gastric cancer cells, tumor cells sporadically developed short, spindle-like morphological characteristics and demonstrated enhanced proliferation and invasive potential. Furthermore, the transformed tumor cells demonstrated decreased tumor formation and increased lymphomatic and intestinal metastatic potential. Non-transformed BGC-823 cells, in contrast, demonstrated primary tumor formation and delayed intestinal and lymph node invasion. We also observed E-cadherin loss and the upregulation of vimentin expression in the transformed tumor cells, which suggested that the increase in metastasis was induced by epithelial-to-mesenchymal transition.
Collectively, our data indicated that normal fibroblasts sufficiently induce epithelial-to-mesenchymal transition in cancer cells, thereby leading to metastasis.
肿瘤在充满病理生理和生物力学信号的三维环境中被认为是一种异质性复合体。细胞与基质的相互作用引导肿瘤的发展和产生。在此，我们评估正常成纤维细胞对胃癌的作用。
方法/主要发现：通过将正常成纤维细胞与BGC - 823胃癌细胞单层共培养，肿瘤细胞偶尔会出现短的、纺锤样形态特征，并表现出增强的增殖和侵袭潜能。此外，转化后的肿瘤细胞显示出肿瘤形成减少，而淋巴和肠道转移潜能增加。相比之下，未转化的BGC - 823细胞表现出原发性肿瘤形成以及肠道和淋巴结侵袭延迟。我们还观察到转化后的肿瘤细胞中E - 钙黏蛋白丢失和波形蛋白表达上调，这表明转移增加是由上皮 - 间质转化诱导的。
总体而言，我们的数据表明正常成纤维细胞足以诱导癌细胞发生上皮 - 间质转化，从而导致转移。
