Abstract 2566: Dissecting PDAC cell-microenvironment interplay in liver metastasis by single cell analysis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. Because most PDAC patients are diagnosed with an already advanced and metastatic stage of the disease, only 15% are suitable for surgical intervention. Thus, an improved understanding of the metastatic mechanism is critical to improve the outcome of these patients. The most common target for PDAC metastasis is the liver. Outgrowth of metastases requires acquisition of tumor genetic alterations in conjunction with alterations in the pancreas and liver microenvironment. The aim of the study was to investigate the role of the tumor microenvironment and the molecular alterations in tumor and stroma cells leading to PDAC liver metastasis formation. To this purpose a metastatic cell variant was established from the FC1199 pancreatic cancer cell line, derived from tumors arisen in LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre mice and growing orthotopically in C57BL/6 mice. The FC199LV metastatic variant was obtained by successive rounds of in vivo selection of cells implanted in the pancreas, isolated from liver metastases and re-implanted in the pancreas for a total of 5 rounds. IHC and in vivo MicroCT analysis of livers at different time points after tumor cell injection highlighted the presence of metastases only in mice transplanted with FC1199LV. Single cell RNA-sequencing analysis of dissociated primary tumors and livers of mice transplanted with FC1199 and FC1199LV highlighted differences in the microenvironmental transcription profile between the two tumor variants. The spontaneous metastatic model of PDAC is an important tool to study the interplay between tumor and stroma in PDAC metastatic process and to identify a tumor and tumor microenvironment gene expression signature associated with PDAC liver metastasis. Supported by AIRC IG 2019 ID23443 Citation Format: Claudia Fioravanti, Arianna Vallerga, Giulia Garattini, Ilaria Craparotta, Federica Di Leva, Chiara Grasselli, Fabio Sangalli, Andrea Resovi, Raffaella Giavazzi, Marco Bolis, Giulia Taraboletti, Dorina Belotti. Dissecting PDAC cell-microenvironment interplay in liver metastasis by single cell analysis [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 2566.