Chemokines induce the cellular migration of MCF-7 human breast carcinoma cells: Subpopulations of tumour cells display positive and negative chemotaxis and differential in vivo growth potentials

We previously reported that chemotactic cytokines (chemokines) induce the d irectional migration of cells derived from the breast carcinoma cell line M CF-7 in vitro, however it was apparent that only a small percentage of cell s displayed the ability to migrate upon stimulation. In the present study t hree sub-lines derived from the parental MCF-7 cell line were selected for their ability to migrate in response to MIP-1 alpha, MIP-1 beta or RANTES a cross Transwell filters of 8 mu m pore size. The first round selection of m igratory cells resulted in sub-populations which demonstrated an increased chemotactic response compared with parental cells. Cells migrating to MIP-1 beta were subjected to four further rounds of positive or negative selecti on, resulting in two sub-lines, MCF-7L4 and MCF-7U4 which displayed an incr eased and decreased chemotactic response respectively to MIP-1 alpha MIP-1 beta and RANTES. No difference in chemokine receptor RNA message expression between these sub-lines and the parental MCF-7 line were detected, althoug h increased levels of alpha 3, alpha 6 and alpha v integrin sub-units were shown for MCF-7L4 (positively selected sub-line) compared with MCF-7U4 cell s. Moreover, the in vivo growth of cells derived from the two MCF-7 sub-lin es was inversely correlated with their chemotactic response. The results of this study depict further the inherent heterogeneity in cancer, suggesting that the chemotactic response may influence the migratory traits of sub-po pulations within the tumour and potentially contribute to their in vivo beh avior, growth and survival.