Abstract 1949: Mouse model of metastatic colorectal cancer by orthotopic transplantation of patient derived organoids

Abstract

Abstract Cancer metastasis proceeds through multiple steps and metastatic colonization is formed by disseminated tumor cells with proliferative capacity in distant tissues. In the analysis of metastasis, macroscopically completed lesions are often used for subjects, which is attributed to the difficulty to capture the early process occurring in living body and the analysis using human specimen is particularly limited. To capture the metastatic process of colorectal cancer (CRC) and to identify cell population involved in it, we produced the mouse model for CRC by orthotopic transplantation of patient derived organoids (PDOs). Unlike ectopic transplantation models, this model precisely recapitulates the metastasis process in human patients. To evaluate the metastasis potentials, the patient matched organoids from the primary, the synchronous liver metastasis and the post-chemotherapy liver recurrence lesion were established. No significant difference in macroscopic morphology or pathogenic mutations were noted among the organoids. The organoids were marked by fluorescent protein and luciferase fusion gene to be visualized the process over time by in vivo imaging system and injected under rectal mucosa on prolapse. Each graft reflected histopathological feature of the surgical specimen. At the results of observation, the lung metastases were frequently occurred in recurrence organoids mouse models, but little occurred in primary or metastasis ones. The lung metastases were considered to be in the early stage of metastasis, because they spread diffusely in each lung lobes, and could not be confirmed macroscopically. They were forming two state; one appeared to be the embolism in blood vessels around the bronchus and others were the micro-metastases in lung tissue. The orthotropic transplantation of patient-matched PDOs provides unique opportunities to explore the metastasis process of CRC. Citation Format: Takuya Okamoto, Katsuyuki Yaginuma, Satoshi Nagayama, Ryoji Yao. Mouse model of metastatic colorectal cancer by orthotopic transplantation of patient derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1949.