Metabolic Cooperation between Mouse Mammary Tumor Subpopulations in Three-Dimensional Collagen Gel Cultures

Abstract

A series of subpopulation lines derived from a single mouse mammary tumor were tested for their ability to interact with each other in metabolic cooperation assays in three-dimensional collagen gel cultures. Inhibition of growth in the presence of selective drug (6-thioguanine or 2-fluoroadenine) of two 6-thioguanine-resistant cell lines, 66cl4 and 44FTO, as well as a 2-fluoroadenine-resistant line, 168FAR, occurred in the presence of other sensitive cells, demonstrating the transfer of drug sensitivity to drug-resistant cells. Transfer of drug resistance was shown by using selective medium containing hypoxanthine, aminopterin, and thymidine plus ouabain in which mutual metabolic cooperation..