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

使用小鼠乳腺肿瘤模型研究肿瘤细胞/细胞相互作用

• 批准号: 08671337
• 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 Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671337/
• 关键词: Mouse mammary tumor; Heterogenity; Hormone-dependency; Autonomous growth; Tumor-cell; cell interactions; Malignancy; Collagen gel; Methallotionein

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.

T4-O1320(320)和T4-O196(96)是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而建立的自治亚系。这些自主肿瘤的特征是在DDD处女鼠中生长迅速，而亲本T4在它们中不生长。在三维胶原凝胶培养中，320细胞形成与正常乳腺相似的分枝或星状结构，但96细胞生长为圆形团块，有结节，形态完全不同。将胶原酶解离后的320、96细胞单独培养或共培养，以确定肿瘤细胞/细胞间是否存在相互作用对生长速度和形态的影响。然而，单一培养和共培养之间的显著差异并没有被研究，这表明了技术改进的必要性。因此，我们研究了这些细胞中甲醇胺的存在是否不同。这种金属结合蛋白是与肿瘤细胞异质性相关的候选因子，据报道与抗肿瘤药物的耐药性有关。用免疫组织化学方法对该蛋白进行了研究。观察到该蛋白水平在恶性程度较低的亚系肿瘤中较低。方法蛋白可能是研究肿瘤细胞恶性程度和异质性的有用因素。这一体外系统在人类乳腺癌中的应用正在进行中。

项目成果

Shimizu M., Yamamoto A., Nakano H., and Matsuzawa A.: "Augmentation of antitumor immunity with bacterial superantigen Staphylococca1 enterotoxin B-bound tumor cells." Cancer Res.56. 3731-3736 (1996)

Shimizu M.、Yamamoto A.、Nakano H. 和 Matsuzawa A.：“利用细菌超抗原葡萄球菌 1 肠毒素 B 结合肿瘤细胞增强抗肿瘤免疫力。”

Shimizu, M., Yamamoto, A., Nakano, H., and Matsuzawa, A.: "Augmentation of antitumor immunity with bacterial superantigen staphylococcal enterotoxin B-bound tumor cells." Cancer Res.56. 3731-3736 (1996)

Shimizu, M.、Yamamoto, A.、Nakano, H. 和 Matsuzawa, A.：“利用细菌超抗原葡萄球菌肠毒素 B 结合肿瘤细胞增强抗肿瘤免疫力。”

Kizu R., Takeda Y.et a1: "An orally active antitumor cyclohexanediamine-Pt(IV)comp1ex:trans,cis,cis-bis(n-valerato)(oxalato)(1R,2R-cyclohexanediamin)Pt(IV)" Anti-cancer Drugs. 7. 248-256 (1996)

Kizu R.、Takeda Y.et a1：“一种口服活性抗肿瘤环己烷二胺-Pt(IV)comp1ex：反式，顺式，顺式-双(n-戊酸)(草酸)(1R,2R-环己烷二胺)Pt(IV)”

Shimizu M.,Yamamoto T.,Nagata S.and Matsuzawa A.: "A trial to kill tumor cells through Fas(CD95) mediated apoptosis in vivo." Biophys.Res.Commun.228. 375-379 (1996)

Shimizu M.、Yamamoto T.、Nagata S. 和 Matsuzawa A.：“通过 Fas (CD95) 介导的体内细胞凋亡杀死肿瘤细胞的试验。”

Matsuzawa A.and Takeda Y.: "Estabhshment of tumor dorment state following clinically complete cure of disseminated leukemin by chemotherapy in mice." In “Premalignancy and Tumor Dormancy"eds.R.H.Schenermann and E.Yefenof.R.G.Landes Company, 15 (1996)

Matsuzawa A. 和 Takeda Y.：“在小鼠中通过化疗临床完全治愈播散性白血病后建立肿瘤休眠状态”，R.H.Schenermann 和 E.Yefenof.R.G.Landes Company 编辑，15（1996 年） ）