Demonstration of a positive feedback loop of paracrine growth stimulation in a new co-culture model of breast cancer

Abstract

A serum-free co-culture model of breast cancer was established using primary cultures of human fibroblasts and the breast cancer lines MCF-7, T47D and MDA-MB-231. The model was used to test the hypothesis that there is a positive feedback loop of paracrine growth stimulation between stromal fibroblasts and cancer cells. Cancer cell growth was dependent on co-culture with fibroblasts and fibroblast growth, in turn, was dependent on co-culture with cancer cells. Platelet derived growth factor (PDGF) was mitogenic for fibroblasts in mono-culture but not mitogenic for cancer cells. However, addition of PDGF to a co-culture of cancer cells with fibroblasts resulted in increased growth of the cancer cells, as predicted by the paracrine loop hypothesis. This model demonstrates one way in which benign stromal cells may be actively recruited into the malignant process.