Abstract 6718: Analysis of the pathological significance of CD109 in pancreatic cancer using the mouse model

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a high fatality rate. Because there are few effective treatments for advanced pancreatic cancer, the development of new molecular targeted therapies is desired. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. We recently reported that positive expression of CD109 in tumor cells was significantly associated with poor prognosis in PDAC. In addition, CD109 expression was also detected in the stroma surrounding the tumor cells, suggesting its expression in cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC. In the present study, we aimed to further investigate the histopathological and prognostic significance of CD109 in PDAC using the mouse model. In the normal mouse pancreas, CD109 expression was almost undetectable by X-gal staining and in situ hybridization. In the PDAC tissues, CD109 expression was detected not only in the tumor cells but also in the surrounding stromal cells, which was similar to that in human PDAC. CD109 expression was predominantly detected in undifferentiated tumor cells rather than differentiated tumor cells. In addition, we generated a CD109-deficient PDAC mouse model line, KPC-CD109KO, and it was revealed that CD109-deficinet KPC mice tended to develop differentiated adenocarcinomas compared with KPC mice with wild-type CD109. However, CD109 deficiency did not affect the survival of KPC mouse. Taken together, CD109 is expressed not only in the tumor cells but also in the stroma in PDAC, and is associated with tumor differentiation in PDAC. Citation Format: Yoshiki Murakumo, Yasutaka Sakurai, Masaaki Ichinoe. Analysis of the pathological significance of CD109 in pancreatic cancer using the mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6718.