Coculture Inserts Possess an Intrinsic Ability to Alter Growth Regulation of Human Breast Cancer Cells

Abstract

Coculture systems are used for a wide variety of cell-cell communication studies. The results reported here reveal that the microporous polycarbonate membranes used in the coculture inserts can remove inhibitory biological macromolecules, resulting in increased cell growth. This provides a cautionary tale to all who use such coculture systems. For estrogen-sensitive breast cancer cells, the use of such membranes results in an increased growth in the absence but not in the presence of estradiol. These effects occurred reproducibly both in the presence of serum and in serum-free medium. Using MCF7 McGrath human breast cancer cells, the up-regulation of basal cell growth in the presence of the coculture insert and serum could be reduced upon blockade of the type I insulin-like growth factor receptor. Ligand blotting experiments revealed that these insert membranes could bind out insulin-like growth factor binding proteins (IGFBP) and remove IGFBP from the culture medium. This suggests a role for IGFBP in the regulation of MCF7 breast cancer cell growth. The molecular and clinical implications are discussed.