Objectives: The molecular mechanisms involved in the regulation of gastric cancer progression by CAFs are still unclear. The aim of the present study was to determine if CAFs can enhance the tumor epithelial-to-mesenchymal transition (EMT) and invasion of gastric cancer cells, and link CAFs with activation of the IL-6/JAK/ STAT3 signaling pathway in the progression of gastric cancer.

Methods: Fibroblasts were isolated from gastric cancer. The identification of CAFs was defined by immunofluorescence staining and qRT-PCR. IL-6 expression in CAFs and gastric cancer cells was detected by qRT-PCR and ELISA. EMT and activation of Stat3 pathway in gastric cancer cells were detected by realtime PCR and western blot. Cell invasion assays were performed by using 8 μm transwell chambers.

Results: IL-6 expression in gastric cancer tissue was significantly higher than that in adjacent non-tumor tissue (3.450ng/g vs 2.665ng/g,P<0.01). Using real time RT-PCR and ELISA, we found IL-6 expression was significantly higher in CAFs compared to that in gastric cancer cells. Co-culture with CAFs in a transwell system induced EMT of gastric cancer cells, which was demonstrated by decreased expression of E-cadherin and α-catenin, and increased expression of Twist1, MMP2 and ZEB2. However, deprivation of IL-6 using a neutralizing antibody or inhibition Stat3 activation with AG490 impaired the EMT of gastric cancer cells. Gastric cancer cells co-cultured with CAFs showed enhanced ability of migration and invasion than gastric cancer cells alone. However, adding neutralizing IL-6 antibody or AG490 into the co-culture system led to significantly decreased invasion (P < 0.05) of SGC-7901 cells. Moreover, IL-6 secreted from CAFs activated the JAK/STAT3 pathway in gastric cancer cells, however, EMT and invasion of gastric cancer cells was inhibited when IL-6/JAK/STAT3 pathway was blocked.

Conclusions: CAFs induced EMT and invasion of gastric cancer cells through activation of the IL-6/JAK/STAT3 pathway.

Citation Format: Liping Su, Xiongyan Wu, Quan Zhou, Chenchen Wang, Bingya Liu. Cancer-associated fibroblast promotes gastric cancer invasion and epithelial-mesenchymal transition via the IL-6/JAK/STAT3 signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4803. doi:10.1158/1538-7445.AM2014-4803

©2014 American Association for Cancer Research.
2014