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How Little Is Too Much? How Transient Tumor-Stromal Crosstalk Can Control Tumor Progression

Christina H. Stuelten

Tumorigenesis is driven by genetic and physiological alterations of tumor cells as well as by the host microenvironment. In a co-culture of breast cancer cells and fibroblasts, short term interactions between tumor cells and stromal fibroblasts increase levels of active, fibroblast derived TGF-β in the extracellular medium, which in turn induces an expanded metastatic pattern of MCF10CA1a cells. These findings suggest that the effects of stromal TGF-β on tumor cell phenotype can be modeled as a dynamical system rather than a continuous linear system. In such a model, small changes of certain parameters of a system that is at a critical point can cause sudden changes of the system, explaining why experimentally and clinically observed small changes in the tumor environment can cause dramatic changes in cell phenotype or disease outcome.