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Study of Tumor Progression in vivo and in vitro using

使用体内和体外肿瘤进展研究

基本信息

批准号：
06671186
负责人：
TAKEDA Yasutaka
金额：
$ 1.41万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Five autonomous sublines, T4-OI320 (329), T4-OI320CY (320CY), T4-OI165 (165), T4-OI145 (145), and T4-OI96 (96), were established from the transpalantable 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. Thus, 10^5320,210^4320CY,2*10^3165,2*10^3145 and 10^396 cells were co-injected with 5*10^5T4 cells into virgin mice to determine whether hormone-dependent tumor cells influence the growth of autonomous tumor cells or not. T4 cells retarded the growth of 320 and 320CY tumors but accelerated that of 165,145 and 96. Irradiated T4 cells stimulated the growth of all the sublines but 320. In three-dimensional collagen gel culture, 320 and 320CY cells formed branched or stellate structures similar to normal mammary glands as did T4, but 165,145 and 96 cells grew as rounded masses with knobs and showed completely different morphology. 165,145 and 96 cells but not the others had lung-colonizing capability. In the collagen gel culture system, an antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the metastatic than on the parent and non-metastatic tumors. Thus, the susceptibility of autonomous subline tumor cells to the growth-inhibitory regulation from the parenetal hormone-dependent tumor cells was well correlated with growth morphology within collagen gels and metastatic property. The results suggest that metastatically-competent tumor cell variants, once they appear, may have a growth advantage in hormone-dependent mammary tumors. Application of this in vitro sytem to human breast cancer is in progress.

以TPDMT-4（T4）为材料，通过不同条件传代，建立了T4-OI 320（329）、T4-OI 320 CY（320 CY）、T4-OI 165（165）、T4-OI 145（145）和T4-OI 96（96）五个自主亚系。这些自主肿瘤的特征是在DDD处女小鼠中快速生长，而亲代T4小鼠中没有生长。因此，将10^5320、210^4320CY、2 * 10^3165、2 *10^3145和10^396个细胞与5* 10^5个T4细胞共注射到未交配的小鼠体内，以确定依赖性肿瘤细胞是否影响自主肿瘤细胞的生长。T4细胞对320和320 CY肿瘤生长有抑制作用，对165、145和96肿瘤生长有促进作用。辐照的T4细胞刺激了除320以外的所有亚系的生长。320和320 CY细胞在三维胶原凝胶培养中形成类似于正常乳腺的分枝状或星状结构，但165、145和96细胞生长为圆形团块，并有结节，显示完全不同的形态。165、145和96细胞具有肺定殖能力，其余细胞无肺定殖能力。在胶原凝胶培养系统中，抗生素蛋白酶抑制剂对转移瘤的生长抑制作用强于对母体和非转移瘤的生长抑制作用。因此，自主亚系肿瘤细胞对来自亲代肿瘤细胞依赖性肿瘤细胞的生长抑制调节的敏感性与胶原凝胶内的生长形态和转移性质密切相关。结果表明，具有转移能力的肿瘤细胞变体一旦出现，可能在乳腺癌依赖性乳腺肿瘤中具有生长优势。这种体外系统在人乳腺癌中的应用正在进行中。