Site-specific experimental metastasis patterns of two human breast cancer cell lines in nude rats.

Abstract

Animal models for breast cancer metastasis are valuable tools for studying mechanisms of metastasis and for preclinical testing of anti-metastatic therapy regimens. Using MA-11 and MT-1, two oestrogen and progesterone receptor-negative human breast cancer cell lines, we developed new models in nude rats with patterns of experimental metastasis resembling those frequently observed in humans. MA-11 cells showed a clear preference for growth in the CNS. Fourteen of 15 animals injected with MA-11 cells into the left ventricle of the heart developed hind-leg paralysis, and tumours were observed in the spinal cord. MT-1 cells consistently exhibited bone/bone marrow metastases after intracardial injection, in addition to tumours in the brain and spinal cord. When injected into the cisterna magna, both cell lines gave rise to leptomeningeal neoplastic disease. Injection of MA-11 cells into the tibial bone marrow resulted in tumours in only 2 of 13 rats, whereas all animals injected with MT-1 cells developed tumours. Only 2 of 6 rats injected i.v. with MA-11 cells developed lung colonies compared with all 9 animals injected with MT-1 cells. Cell-surface expression of the following was examined: EGP2; MUC1; EGFr; E- and N-cadherin; the alpha2, alpha3, alpha5, beta1 and beta4 integrins; c-erb-B2; and N-CAM. c-erb-B2 was expressed in a higher percentage of the bone-metastasizing MT-1 cells than the MA-11 cells, whereas E-cadherin was expressed in MA-11 but not MT-1 cells. In animals injected with MA-11 and MT-1 cells in the left cardiac ventricle, treatment with cisplatin and doxorubicin did not improve survival. In summary, these clinically relevant animal models may be used for studies related to site-specific growth and metastasis and for assessing effects of experimental therapy against human breast cancer.