Abstract 3311: Autologous colorectal cancer-mesothelial co-culture model identifies stromal FGFR3 dependency driving peritoneal dissemination

Abstract Background: Peritoneal dissemination of colorectal cancer (CRC) remains a fatal disease with limited therapeutic options. Mesothelial cells, which line the peritoneal cavity, play critical roles in metastatic implantation and stromal remodeling, yet the mechanisms governing tumor-stroma interactions in this setting remain poorly understood. We aimed to establish a physiologically relevant model to elucidate these interactions and identify stromal vulnerabilities. Methods: We simultaneously derived a novel CRC cell line (OMUCR-1) and cancer-associated mesothelial cells (CAmeso) from the malignant ascites of a single patient with metastatic CRC. As a control, normal mesothelial cells (Nmeso) were established from a patient without dissemination. Cell morphology, growth kinetics, STR profile, and mutational status were characterized. The effects of CAmeso on CRC migration and invasion were evaluated using wound-healing and Matrigel assays. In vivo, OMUCR-1 cells were implanted alone or co-transplanted with CAmeso into nude mice. RNA sequencing was performed to analyze host stromal gene expression, and FGFR inhibition (BGJ398) was tested therapeutically. Results: OMUCR-1 cells exhibited robust tumorigenicity and harbored KRAS (G12D) and TP53 (R306) mutations. CAmeso significantly enhanced CRC cell migration and invasion in vitro. In xenografts, co-transplantation with CAmeso yielded markedly larger tumors enriched in αSMA-positive stroma compared with OMUCR-1 alone. Bulk RNA-seq revealed upregulation of murine Fgfr3 in tumors containing CAmeso. Pharmacologic FGFR blockade with BGJ398 reduced tumor size and depleted FGFR3-positive stromal components, indicating stromal FGFR3 dependency. Conclusions: We report the first concurrent establishment of CRC and mesothelial cell lines from the same patient, providing an autologous system for dissecting tumor-stroma crosstalk during peritoneal metastasis. Our findings highlight stromal FGFR3 signaling as a potential mediator of CRC progression and a promising target for therapeutic intervention. This unique platform offers a valuable resource for mechanistic and translational studies on the peritoneal microenvironment in advanced colorectal cancer. Citation Format: Hiroaki Kasashima, Yasuhiro Fukui, Iguru Omori, Zizhou Wang, Nobuhiro Naito, Yukina Kusunoki, Kenji Kuroda, Yuichiro Miki, Mami Yoshii, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Masakazu Yashiro, Yuki Nakanishi, Naoko Ohtani, Kiyoshi Maeda. Autologous colorectal cancer-mesothelial co-culture model identifies stromal FGFR3 dependency driving peritoneal dissemination abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3311.