Figure 5. Reversibility of coculture-induced changes in cell cycle.

A. Comparative cell cycle profiles of grade 1 and grade 3 tumor cells after 7-day fibroblast coculture, followed by a 48 hr period without coculture. Note marked reduction in the G2 population of the grade 1 cell line upon termination of coculture conditions. Both control and test populations display signs of G0/G1 arrest due to culture confluence. In the grade 3 tumor line, post coculture cell cycling returns to control profiles. Numbered pie chart segments indicate the percentage of cells in G1 and S phase. SubG1: yellow; G1: green; S: red; G2/M: blue. B. The FTExT model : through the application of live interactive cocultures of stromal fibroblasts and primary tumor-derived epithelium of varying histologic grade, FTExT offers novel insights into the biological basis of grade-associated stratification of primary breast cancer. It proposes that cell lines derived from well-differentiated tumors associated with good clinical prognosis recapitulate their functional characteristics in the presence of stromal fibroblasts in vitro. Similarly, tumor cells derived from poorly differentiated malignant lesions retain the contextual ability to respond to the same paracrine influence in a manner corresponding to cancer aggressiveness and unfavorable patient outcome. Such authentic model systems are an essential tool for advancing the goals of research in cancer biology.