INVESTIGATION OF MAMMARY EPITHELIAL CELL-BONE MARROW STROMA INTERACTIONS USING PRIMARY HUMAN CELL-CULTURE AS A MODEL OF METASTASIS

A model has been established using primary human cell culture to study the cell biology of breast cancer metastasis to bone marrow. Mammary epithelia were obtained in single cell suspension from tumour (macrosc opically involved), benign (macroscopically uninvolved) and normal (re duction mammoplasty) breast tissue as well as from locally involved ly mph nodes. Stromal layers were generated from long-term cultures of hu man bone marrow or from mammary fibroblasts derived from normal or mal ignant tissue. The interaction between epithelia and stroma has been s tudied in terms of adhesion of the epithelia to the stroma and their s ubsequent growth in co-culture. Our results show that when assayed up to 9 hr after plating, epithelial cells from malignant tissue (14 prim ary tumours and 9 metastases in lymph nodes) displayed a significant p reference for adhesion to bone marrow stroma compared with mammary fib roblasts. In contrast, epithelial cells from 4 normal and 2 of 4 benig n samples showed no significant preferential adherence. Subsequent co- culture of mammary epithelia with each of the 3 stromal layers reveale d that under serum-free, in vitro conditions, bone marrow stromal laye rs did not provide an advantageous environment for colony growth, in c ontrast to their ability to provide a preferential substratum for adhe sion. (C) 1997 Wiley-Liss, Inc.