Establishment of an Orthotopic and Metastatic Colorectal Cancer Mouse Model Using a Tissue Adhesive-Based Implantation Method

초록

Simple Summary Orthotopic and metastatic mouse models of colorectal cancer are essential tools for studying tumor progression and evaluating therapeutic strategies. However, conventional modeling techniques such as syringe injection or surgical suturing often result in variable engraftment efficiency, technical complexity, and limited metastatic reliability. Mouse models are widely used to study how colon cancer spreads to other organs and to test potential new treatments. In this study, we developed a simplified and reliable method to transplant colon cancer tissue into mice using a special biological bond. This approach led to consistent tumor growth and spread to the liver and lungs, helping researchers study cancer progression and drug effects more effectively. Background: To overcome the limitations of conventional CRC (colorectal cancer) mouse models in replicating metastasis and enabling efficient therapeutic evaluation, we developed a novel implantation method using tissue adhesive to establish reproducible orthotopic and metastatic tumors. Conventional models using injection or suturing techniques often suffer from technical complexity, inconsistent tumor establishment, and limited metastatic reliability. Methods: We developed and validated a novel orthotopic and metastatic CRC model utilizing tissue adhesive for tumor transplantation. Uniform tumor fragments derived from bioluminescent HCT116/Luc xenografts were affixed to the cecum of nude mice. Tumor growth and metastasis were monitored through bioluminescence imaging and confirmed by the results of histological analysis of metastatic lesions. The model's utility for therapeutic testing was evaluated using MK801, an NMDA receptor antagonist. Results: The biological-based model demonstrated rapid and reproducible tumor implantation (<5 min), consistent primary tumor growth, and robust metastasis to the liver and lungs. The biological-based approach achieved 80% tumor engraftment (4/5), with consistent metastasis to the liver and lungs in all mice, compared with lower and variable metastasis rates in injection (0%, 0/5) and suturing (20%, 1/5) methods. MK801 treatment significantly suppressed both primary tumor growth and metastasis, validating the model's suitability for preclinical drug evaluation. Conclusions: By enabling rapid, reproducible, and spontaneous formation of metastatic lesions using a minimally invasive tissue adhesive technique, our model represents a significant methodological advancement that supports high-throughput therapeutic screening and bridges the gap between experimental modeling and clinical relevance in colorectal cancer research.

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