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.

Abstract

We previously reported that chemotactic cytokines (chemokines) induce the directional migration of cells derived from the breast carcinoma cell line MCF-7 in vitro, however it was apparent that only a small percentage of cells displayed the ability to migrate upon stimulation. In the present study three sub-lines derived from the parental MCF-7 cell line were selected for their ability to migrate in response to MIP-1alpha, MIP-1beta or RANTES across Transwell filters of 8 microm pore size. The first round selection of migratory cells resulted in sub-populations which demonstrated an increased chemotactic response compared with parental cells. Cells migrating to MIP-1beta were subjected to four further rounds of positive or negative selection, resulting in two sub-lines, MCF-7L4 and MCF-7U4 which displayed an increased and decreased chemotactic response respectively to MIP-1alpha MIP-1beta and RANTES. No difference in chemokine receptor RNA message expression between these sub-lines and the parental MCF-7 line were detected, although increased levels of alpha3, alpha6 and alphav integrin sub-units were shown for MCF-7L4 (positively selected sub-line) compared with MCF-7U4 cells. Moreover, the in vivo growth of cells derived from the two MCF-7 sub-lines 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-populations within the tumour and potentially contribute to their in vivo behavior, growth and survival.