Abstract 2125: Cancer-associated fibroblasts-stimulated IL-11 promotes metastasis of gastric cancer cells mediated by upregulation of MUC1

Abstract

Abstract Background: Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma and regulators of tumor progression. However, the molecular mechanism by which CAFs promote gastric cancer progression should be further explored. Methods: Mouse model was used to certify that CAFs could promote peritoneal metastasis of gastric cancer cells. The expression of interleukin-11 (IL-11) was analyzed in two gastric cancer cell lines by real-time RT-PCR and ELISA. The role of IL-11 in gastric cancer cell migration and invasion explored by Transwell. Western blotting was conducted to detect the activation of STAT3 and ERK signaling pathway. Results: In our study, we reveal that when CAFs co-cultured with gastric cancer cells secreted significant amounts of IL-11. CAFs promote the ability of migration and invasion through the production of IL-11 by stimulating JAK/STAT3 and MAPK/ERK pathways to upregulate MUC1 in gastric cancer cells. On the other hand, when IL-11 was deprived using a neutralizing antibody or inhibition of JAK/STAT3 and MAPK/ERK pathways with specific inhibitors, Stattic and PD-98059, markedly attenuated these CAFs-induced phenotypes in gastric cancer cells. Conclusions: Taken together, these results revealed that CAFs play a significant role in the gastric cancer progression in the tumor microenvironment through IL-11-STAT3/ERK signaling by upregulating MUC1. Also, IL-11 targeted therapy can achieve an effective treatment against gastric cancer indirectly by exerting their action on stromal fibroblasts. Citation Format: Xiaoxun Wang, Xiaofang Che, Ming Bai, Yibo Fan, Yunpeng Liu, xiujuan qu. Cancer-associated fibroblasts-stimulated IL-11 promotes metastasis of gastric cancer cells mediated by upregulation of MUC1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2125.