INTERACTION BETWEEN TUMOR ITS MICROENVIRONMENT AVNER FRIEDMAN Mathematical

INTERACTION BETWEEN TUMOR & ITS MICROENVIRONMENT AVNER FRIEDMAN Mathematical Biosciences Institute Ohio State University, Columbus, USA

Thin slice of a breast tumor Background on Breast Cancer http: //www. jamesline. com/images/frontiers/summer 2005/Partners. In. Crime 1. jpg ● Epithelial cells are transformed by gene mutations (TECs). ● TECs secrete TGF-ß (transforming growth factor beta). ● TGF-ß signals to fibroblasts which get transformed to myofibroblasts; both secrete EGF (epidermal growth factor). ● Fibroblasts/myofibroblasts form the microenvironment of the tumor ● We want to examine how they interact with the TECs at the very early stage of cancer.

Complex pathways stimulating cell proliferation EGF, RAS, MAPK TGF-b, SMAD biocarta. com

TRANSFORMED EPITHELIAL CELLS (TECs)

EXPERIMENT & MODEL DOMAIN MEMBRANE fibroblasts myofibroblasts ( TECs ) MEMBRANE ● Place TECs in solution at bottom of well. ● Place semi-permeable membrane above the solution. ● Deposit fibroblasts/myofibroblasts above the membrane. ● Count the number of TECs in day 2, 4, 6, and 8. ● TGF-ß and EGF can cross the membrane, but cells cannot. - + fibroblasts ( f ) myofibroblasts ( m ) EGF (E) TEC ( n ) EGF (E) TGF-b (G) X=0

Diffusion of TECs

CHEMOTAXIS : n cells move towards increasing concentration of EGF

Cell proliferation : logistic growth enhanced by EGF via Hill-type kinetics

production of EGF by fibroblasts & myofibroblasts in -

on the semi-permeable membrane

● Having gained understanding of the early stage of breast cancer in vitro without ECM, the next step is to include ECM, using the value of g that was established.