Wittmer A, Khazaie K, Berger M R
Unit of Toxicology and Chemotherapy, German Cancer Research Center (DKFZ), Heidelberg.
Clin Exp Metastasis. 1999 Jul;17(5):369-76. doi: 10.1023/a:1006643831825.
Disseminated colon carcinoma metastases in the liver are associated with low cure rates and constitute a serious therapeutic problem. Appropriate experimental models which mimic metastases development and outgrowth can provide insight into the mechanism of this lethal process and facilitate the finding of new approaches for its control. We established an orthotopic liver metastases model based on CC531 rat colon adenocarcinoma cells which were transfected with a beta-galactosidase gene as marker to facilitate their detection. Intraportal injection of CC531-lac-Z cells resulted in a rapid and locally aggressive growth within the liver and was characterised by a tumour volume doubling time of 20 h and abundant angiogenesis. A commercially available chemi-luminescence assay allowed rapid, quantitative and sensitive detection of the diffusely growing tumour cells. Immunogenicity of CC531-lac-Z cells induced by the marker gene was significantly reduced by co-administering the tumour cells with matrigel. Within an observation period of three weeks following tumour cell injection only 6% of the animals showed lung involvement, thus indicating a specific homing of CC531-lac-Z cells to the liver. This period appears long enough to allow therapeutic manipulations at various stages of tumour growth in the liver. It is envisaged that the model will have applications for various therapeutic strategies.
播散性结肠癌肝转移的治愈率低，是一个严重的治疗难题。能够模拟转移发生和发展的合适实验模型有助于深入了解这一致命过程的机制，并促进寻找新的控制方法。我们建立了一种基于CC531大鼠结肠腺癌细胞的原位肝转移模型，该细胞转染了β-半乳糖苷酶基因作为标记物，便于检测。门静脉内注射CC531-lac-Z细胞导致肝脏内快速且局部侵袭性生长，其肿瘤体积倍增时间为20小时，且有丰富的血管生成。一种市售的化学发光检测法能够快速、定量且灵敏地检测弥漫性生长的肿瘤细胞。通过将肿瘤细胞与基质胶共同给药，标记基因诱导的CC531-lac-Z细胞的免疫原性显著降低。在肿瘤细胞注射后的三周观察期内，只有6%的动物出现肺转移，这表明CC531-lac-Z细胞特异性归巢至肝脏。这段时间似乎足够长，能够在肝脏肿瘤生长的各个阶段进行治疗操作。预计该模型将适用于各种治疗策略。
