AN EXPERIMENTAL-MODEL OF LEPTOMENINGEAL METASTASES EMPLOYING RAT MAMMARY-CARCINOMA CELLS

Five percent of patients dying with breast cancer have leptomeningeal metastases (LM) but current therapy is of only marginal benefit. There fore, an experimental model of LM from breast cancer was developed to facilitate the development of novel therapies. Cell suspensions of 137 62 MAT Bill rat mammary carcinoma cells are injected into the cisterna magna of adult, female Fischer 344 rats under general anesthesia. 10- 12 days after the injection of 2 x 10(5) viable cells, animals develop neurologic signs, including ataxia, paralysis and spontaneous rotatio n. Histologically, tumor cells can be seen in the subarachnoid space o ver the surface of the brain and spinal cord and within the ventricles . Tumor cells do not invade the brain parenchyma. Collections of tumor cells are extensively infiltrated by macrophages and CD8-positive (su ppressor/cytotoxic) T cells, but by few CD4-positive (helper) T cells. MAT BIII cells therefore provide a model of LM from breast cancer wit h a reproducible clinical course and histologic features. The tumor el icits a cellular immune response and can be useful in exploring biolog ic therapies for leptomeningeal metastases.