MBI Publications

MBI Publications for Myofibroblasts (2)

  • Y. Kim and A. Friedman
    Interaction of tumor with its microenvironment: A Mathematical Model
    Bulletin of Mathematical BiologyVol. 72 No. 5 (2010) pp. 1029-1068

    Abstract

    This paper is concerned with early development of transformed epithelial cells (TECs) in the presence of fibroblasts in the tumor microenvironment. These two types of cells interact by means of cytokines such as transforming growth factor (TGF-beta) and epidermal growth factor (EGF) secreted, respectively, by the TECs and the fibroblasts. As this interaction proceeds, TGF-beta induces fibroblasts to differentiate into myofibroblasts which secrete EGF at a larger rate than fibroblasts. We monitor the entire process in silico, in a setup which mimics experiments in a Tumor Chamber Invasion Assay, where a semi-permeable membrane coated by extracellular matrix (ECM) is placed between two chambers, one containing TECs and another containing fibroblasts. We develop a mathematical model, based on a system of PDEs, that includes the interaction between TECs, fibroblasts, myofibroblasts, TGF-beta, and EGF, and we show how model parameters affect tumor progression. The model is used to generate several hypotheses on how to slow tumor growth and invasion. In an Appendix, it is proved that the mathematical model has a unique global in-time solution.
  • Y. Kim, J. Wallace, F. Li, M. Ostrowski and A. Friedman
    Transformed Epithelias cells (TEC) and fibroblasts/myofibroblasts interaction in Breast Tumor: A Mathematical Model and Experiments
    Journal of Mathematical BiologyVol. 61 No. 3 (2010) pp. 401-421

    Abstract

    It is well known that tumor and its microenvironment, or stroma, interact with each other and that this interaction plays a critical role in tumor initiation, growth, and metastasis. This interaction consists of complex relations between tumor cells, stromal cells such as fibroblasts, epithelial cells and immunocytes, the vascular system, the extracellular matrix, and cytokines secreted by the cells. Understanding these relationships may lead to new therapeutic approaches to cancer. In the present paper, we consider tumor-stroma crosstalk in a simple in vitro situation which involves interaction between tumor epithelial cells from breast cancer and a microenvironment consisting of just fibroblasts. The two populations of cells are separated by a semi-permeable membrane that allows only cytokines to cross over. We develop a mathematical model that includes two critical growth factors: TGF-beta, produced by the tumor cells, and EGF, secreted by the fibroblasts. The TGF-beta modifies the microenvironment by transforming fibroblasts into myofibroblasts. Myofibroblasts secrete higher concentrations of EGF than fibroblasts, thereby, increasing the proliferation of tumor cells. Thus already in this simple setup one sees a mutual interaction between tumor cells and their microenvironment. We conducted experiments which show good agreement with the model's simulations, hence confirming the model's ability to predict aspects of tumor cell behavior in response to signaling from fibroblasts.

View Publications By