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.
背景：为克服传统结直肠癌小鼠模型在模拟转移及有效治疗评估方面的局限性，我们开发了一种利用组织粘合剂建立可重复性原位及转移性肿瘤的新型植入方法。传统注射或缝合技术模型常存在操作复杂、肿瘤形成不稳定及转移可靠性有限等问题。 方法：我们开发并验证了一种利用组织粘合剂进行肿瘤移植的新型原位转移性结直肠癌模型。将源自生物发光HCT116/Luc异种移植瘤的均质肿瘤片段固定于裸鼠盲肠。通过生物发光成像监测肿瘤生长与转移，并经转移病灶组织学分析结果验证。采用NMDA受体拮抗剂MK801评估该模型在治疗测试中的应用价值。 结果：该生物粘合模型实现了快速（<5分钟）且可重复的肿瘤植入、稳定的原发瘤生长以及向肝脏和肺部的强效转移。与注射法（0%，0/5）和缝合法（20%，1/5）较低且不稳定的转移率相比，生物粘合法达到80%的肿瘤移植成功率（4/5），所有小鼠均呈现稳定的肝肺转移。MK801治疗显著抑制原发瘤生长与转移，验证了该模型在临床前药物评估中的适用性。 结论：通过微创组织粘合技术实现快速、可重复且自发的转移灶形成，本模型代表了重要的方法学进展，可支持高通量治疗筛选，并弥合了结直肠癌研究中实验建模与临床相关性之间的鸿沟。
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