Normal fibroblasts induce E-cadherin loss and increase lymph node metastasis in gastric cancer.

• Main Authors: Wen Xu, Xinlei Hu, Zhongting Chen, Xiaoping Zheng, Chenjing Zhang, Gang Wang, Yu Chen, Xinglu Zhou, Xiaoxiao Tang, Laisheng Luo, Xiang Xu, Wensheng Pan
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2014-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC4028202?pdf=render

BACKGROUND: 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. CONCLUSION: Collectively, our data indicated that normal fibroblasts sufficiently induce epithelial-to-mesenchymal transition in cancer cells, thereby leading to metastasis.