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

Abstract

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.

Lung carcinogenesis and fibrosis taken together

“…Stromal fibroblasts can effect tumor cell behavior in various manners. For instance, fibroblasts of the host environment interact with tumour cells and secrete in the ECM several growth factors like TGF-β, which next enhance a metastatic profile [113, 114]. Moreover, tumour-associated fibroblasts regulate matrix stiffness and, thereby, tumour cells promote angiogenesis [115, 116].…”