A study on tumor cell/cell interactions using mouse mammary tumor models

从可移植的激素依赖性小鼠乳腺肿瘤TPDMT-4（T4）中，通过不同条件传代，建立了自主亚系T4- o1320（320）和T4- o196（96）。这些自主肿瘤在DDD初代小鼠中生长迅速，而亲代T4未生长。在三维胶原凝胶培养中，320个细胞与T4一样形成了类似于正常乳腺的支状或星状结构，但有96个细胞呈圆形团块状，呈结节状，形态完全不同。然后将320和96个细胞分别单独培养或胶原酶解离后共培养，观察肿瘤细胞/细胞之间是否存在生长速率和形态上的相互作用。但单培养与共培养的差异不明显，说明技术有待改进。因此，我们研究了这些细胞之间甲基化肽的存在是否不同。这种金属结合蛋白是研究肿瘤细胞异质性的一个候选因子，据报道与抗肿瘤药物的耐药性有关。用免疫组织学方法对该蛋白进行了研究。在恶性程度较低的亚肿瘤中，该蛋白水平较低。甲基甲氧胺似乎是研究肿瘤细胞恶性和异质性的有用因子。该体外系统在人类乳腺癌中的应用正在进行中。

The autonomous sublines, T4-O1320(320)and T4-O196(96), were established from the transplantable hormone-dependent mouse mammary tumor, TPDMT-4(T4), by passaging under different conditions. These autonomous tumors were characterized by rapid growth in DDD virgin mice and the parental T4 by no growth in them. In three-dimensional collagen gel culture, 320 cells formed branched or stellate structures similar to normal mammary glands as did T4, but 96 cells grew as rounded masses with knobs and showed completely different morphology. Then, 320 and 96 cells were cultured separately or co-cultured after collagenase dissociation to determine whether there are tumor cell/cell interaction on the growth rate and morphology. However, significant differences between single-culture and co-culture were not investigated on them, showing the necessity of improvement of the technology. Therefore, we studied whether the presence of methallotionein are different or not between these cells. This metal-binding protein, a candidate factor to be investigated relative to heterogeneity of tumor cells, is reported to associate with resistance of anti-tumor drugs. This protein was studied by immuno-histological methods. It was observed that the protein level was the lower in the less malignant subline tumors. Methallotionein seems to be a useful factor to investigate malignancy and heterogeneity of tumor cells. Application of this in vitro system to human breast cancer is in progress.