CHARACTERIZATION OF VARIANTS OF A HUMAN BREAST-CANCER CELL-LINE ISOLATED FROM METASTASES IN DIFFERENT ORGANS OF NUDE-MICE

The MDA-MB-435 human breast cancer cell line metastasizes from tumors growing in the mammary fatpad of nude mice; metastases are found in the lymph nodes and lungs of 75 to 100% of tumor-bearing mice, and at a lower incidence in other organs such as the heart, skeletal muscle, adrenal gland and brain. Variants of this breast cancer cell line were established from metastases in different organs, including the lungs and brain of nude mice; these lines were designated 435-Lung2 and 435-Br1, respectively. Karyotypic analysis of the new variants suggested a clonal origin for the different organ metastases. The lung-derived cells were as metastatic as the original cell line when re-injected in nude mice, yet the cells from the brain metastasis produced few metastases. Analyses of the invasive potential of the cell lines showed that they did not differ in expression of mRNA for 72-kDa type IV-collagenase, or in gelatinase activity (by zymography), or in ability to invade through a Matrigel-coated filter. The poorly metastatic 435-Br1 cells showed reduced binding to cultured monolayers of mouse lung-endothelial cells, compared with the metastatic 435-Lung2 and MDA-MB-435 cells. When the breast cancer cells were artificially arrested in the lungs of nude mice, by injecting Cytodex beads coated with cells, all three cell lines grew equally well, suggesting that the deficiency found in the metastatic potential of the 435-Br1 cells may be associated with interactions with endothelial cells, rather than growth potential in the lungs. Further comparisons of these two metastasis-derived variants of a heterogeneous cell line will lead to greater understanding of the metastatic phenotype of human breast cancer.