Abstract 281: The function of FGFR2+ cancer-associated fibroblasts on cancer stem cell expansion of esophageal squamous cell carcinoma

Abstract Aims: FGFR2+ fibroblasts were reported to promote tumor progression, but the mechanisms remained unexplored in esophageal squamous cell carcinoma (ESCC). Methods: Multiplex immunohistochemistry (mIHC) displayed the distributions of FGFR2+ fibroblasts and cancer stem cells (CSCs). After FGFR2+ fibroblast isolation, tumor cells were stimulated with fibroblasts supernatant to assess radioresistance and CSC properties. RNA-seq analysis identified the downstream BMP5 expression. Results: In our preliminary study, the immunohistochemistry results showed that FGFR2+ fibroblasts were always represented in the area near cancer stem cells (CSCs), and FGFR2+ fibroblasts infiltration was associated with poor outcomes. When we cocultured FGFR2+ fibroblasts with tumor cells, we found the proportion of CSCs were upregulated. The results of RNA sequencing and ELISA showed that FGFR2+ fibroblasts overexpressed BMP5. Using FGFR2+ fibroblasts or BMP5 to stimulate cancer cells, the proportion of cancer stem cells was increased, the capabilities of sphere formation and survival after radiation were enhanced. Both RNA sequencing and immunoblotting results indicated that BMP5 affected H2AX phosphorylation in DNA repair pathway and activated its potential upstream pathway MAPK signaling pathway. In vivo experiments also showed that FGFR2+ fibroblasts could upregulate CSCs proportions. Conclusions: Our findings suggested that BMP5 derived from FGFR2+ fibroblasts might induce CSCs expansion and led to poor prognosis in the ESCC. Citation Format: Ying Wang, Ping Feng, Tong-chao Jiang, Xin-yuan Guan, Yun-fei Xia. The function of FGFR2+ cancer-associated fibroblasts on cancer stem cell expansion of esophageal squamous cell carcinoma 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 (6Suppl): Abstract nr 281.