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

Christina H Stuelten

doi:10.4172/2155-9899.1000462

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.

Highlights

Tumorigenesis is driven by genetic and physiological alterations of tumor cells as well as by the host microenvironment
A recent study showed that even transient interactions between tumor cells and fibroblasts can significantly impact tumor progression through a mechanism that is dependent on TGF-β [5]
TGF-β is an important mediator of tumor stromal crosstalk and has been implicated in attracting immune and endothelial cells to the tumor, to activate fibroblasts and to alter tumor cell biology [9]

Summary

Introduction

Tumorigenesis is driven by genetic and physiological alterations of tumor cells as well as by the host microenvironment. In a model of breast cancer, co-cultures of normal fibroblasts and breast cancer cells (MCF10CA1a) secrete small amounts of active TGF-β (0.1–0.2 ng/ml) into the extracellular medium, an effect that is not seen when either cell type is cultured separately [5].

Results

Conclusion