Abstract 6807: Cancer suppressive mechanism of IL-6 secreted by cancer-related fibroblasts in biliary tract cancer

Abstract

Abstract Background and aims: Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and can exhibit cancer-promoting functions; however, recent studies indicate that CAFs can also inhibit cancer growth and progression. In this study, we identified CAFs that act in an inhibitory manner in biliary tract cancer and elucidated their mechanisms. Methods: Three biliary tract cancer cell lines and CAFs isolated from resected specimens from four types of biliary tract cancer were used to evaluate the proliferative potential of cancer cells. Potential suppressors that inhibited the growth of cancer cells were identified using protein arrays from CAFs. We determined the effects of these suppressors on cancer cells. Results: Among the biliary tract cancer CAFs, we identified CAFs that inhibited cancer growth. Protein arrays of conditioned medium from CAFs revealed that Interleukin-6 (IL-6) was one such growth inhibitor. Treatment of biliary tract cancer cell lines with IL-6 significantly reduced their proliferative potential. SOCS3 expression levels increased and STAT3 expression level decreased, suggesting that SOCS3, a downstream signal of IL-6, may be involved. Conclusion: Inhibitory CAFs are present among biliary tract cancer CAFs and IL-6 production by CAFs may inhibit the growth of biliary tract cancer cells. Citation Format: Kenjiro Kimura, Ryota Tanaka, Simpei Eguchi, Kosuke Hatta, Masahiko Kinoshita, Jun Tauchi, HIroji Shinkawa, Kohei Nishio, Go Ohira, Takeaki Ishizawa. Cancer suppressive mechanism of IL-6 secreted by cancer-related fibroblasts in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6807.