INTERACTION BETWEEN TUMOR & ITS MICROENVIRONMENT

AVNER FRIEDMAN

Mathematical Biosciences InstituteOhio State University, Columbus, USA

● 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.

Thin slice of a breast tumor

http://www.jamesline.com/images/frontiers/summer2005/PartnersInCrime1.jpg

Background on Breast Cancer

EGF, RAS, MAPK TGF-, SMAD

Complex pathways stimulating cell proliferation

biocarta.com

TRANSFORMED EPITHELIAL CELLS (TECs)

X = 0

MEMBRANE

EGF (E)

TGF- (G)

fibroblasts ( f )

myofibroblasts ( m )TEC ( n )

fibroblastsmyofibroblasts

EGF (E)

TGF- (G)

EXPERIMENT & MODEL DOMAIN

● 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.

( TECs )

MEMBRANE

- +

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 that was established.