Abstract 2814: Rectal implantation paves the path to evaluate the metabolic machinery responsible for CRC metastasis

Abstract

Abstract Introduction: Colorectal carcinoma patients die most often from distant metastases in liver and lung. It is crucial to develop metastatic models for the CRC in order to better understand the process, which will help in treatment. Method: Using orthotropic transplantation techniques, we tried to test whether rectal implantation could produce spontaneous metastases in-vivo mimicking colorectal cancer. The rectum was injected orthotopically with 0.2 × 106 HCT116 cells. In order to confirm metastasis, histopathological examinations were performed. Further, we generated cancer organoids to evaluate population susceptibility to CRC metastasis and metabolic mechanisms responsible for metastasis process. Results: We found that rectal implantation was an effective method for simulating CRC cancer metastasis using H&E staining and immunohistochemistry. In less than four weeks after the implant, HCT116 spontaneously metastasized to the liver, lungs, and D lymph node. When compared with cancer organoids derived from primary tumors, liver and lung metastases organoids proliferated more often, were more aggressive, and displayed distinct characteristics. Using non-targeting metabolomic analysis, it was found that metastases derived organoids and primary tumors derived organoids were distinguished by novel metabolites. Conclusion: By implantation in the rectal cavity, we can evaluate the metabolic machinery that leads to CRC metastasis. In the future, implantation of patient-derived samples will become increasingly important. Citation Format: Said M. Afify, Chen Shen, Siva B. Merugu, Daniel T. Wynn, Anmada Nayak, Wenhui Lu, Ricardo M. Calderin, Evan Pannkuk, Sung H. Hong, Nagi G. Ayad, David J. Robbins. Rectal implantation paves the path to evaluate the metabolic machinery responsible for CRC metastasis [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(6_Suppl):Abstract nr 2814.