Price J E, Polyzos A, Zhang R D, Daniels L M
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1990 Feb 1;50(3):717-21.
There are few reports describing experimental models of the growth and metastasis of human breast carcinomas. This article discusses the tumorigenic and metastatic properties of two estrogen receptor-negative breast carcinomas injected into nude mice. Tumor growth in the mammary fatpad (m.f.p.) and the subcutis was compared in female nude mice. The injection of 10(5) viable cells of two human breast carcinoma cell lines (MDA-MB-231 and MDA-MB-435) gave a 100% tumor take rate in the m.f.p., whereas only 40% of the s.c. injections produced tumors and these occurred several weeks after the appearance of the m.f.p. tumors. Thus, the m.f.p. of nude mice is a favorable site for the growth of human breast carcinomas. MDA-MB-435 tumors produced distant metastases in 80% to 100% of recipients. The most common sites for metastasis were the lymph nodes and lungs, with a lower incidence of metastases in muscle (chest wall and thigh), heart, and brain. New variant cell lines were isolated from metastases in the lungs, brain, and heart. All the cell lines were tumorigenic in the m.f.p., and the lung- and heart-derived metastasis lines produced slightly more lung metastases than the original cell line. However, the brain metastasis variant produced significantly fewer lung metastases. Intravenous inoculation of the spontaneous metastasis-derived cell lines produced few lung colonies. Only cell variants isolated from experimental lung metastases showed enhanced lung colonization potential when reinjected i.v. Our results suggest that the estrogen receptor-negative MDA-MB-435 cell line injected in the m.f.p. of nude mice could be a valuable tool for analysis of the cellular and molecular basis of the metastasis of advanced breast cancer.
很少有报告描述人类乳腺癌生长和转移的实验模型。本文讨论了将两种雌激素受体阴性乳腺癌注射到裸鼠体内后的致瘤性和转移特性。在雌性裸鼠中比较了乳腺脂肪垫（m.f.p.）和皮下组织中的肿瘤生长情况。注射两种人乳腺癌细胞系（MDA-MB-231和MDA-MB-435）的10(5)个活细胞，在乳腺脂肪垫中的肿瘤接种成功率为100%，而皮下注射只有40%产生肿瘤，且这些肿瘤在乳腺脂肪垫肿瘤出现数周后才发生。因此，裸鼠的乳腺脂肪垫是人类乳腺癌生长的有利部位。MDA-MB-435肿瘤在80%至100%的受体中产生远处转移。最常见的转移部位是淋巴结和肺，肌肉（胸壁和大腿）、心脏和脑的转移发生率较低。从肺、脑和心脏的转移灶中分离出了新的变异细胞系。所有细胞系在乳腺脂肪垫中都具有致瘤性，且源自肺和心脏的转移细胞系产生的肺转移略多于原始细胞系。然而，源自脑转移的变异细胞系产生的肺转移明显较少。静脉接种自发转移衍生的细胞系产生的肺集落很少。只有从实验性肺转移中分离出的细胞变异体再次静脉注射时显示出增强的肺定植潜力。我们的结果表明，注射到裸鼠乳腺脂肪垫中的雌激素受体阴性MDA-MB-435细胞系可能是分析晚期乳腺癌转移的细胞和分子基础的有价值工具。
