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INTERACTION BETWEEN TUMOR & ITS MICROENVIRONMENT

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/summer2005/PartnersInCrime1.jpg.

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INTERACTION BETWEEN TUMOR & ITS MICROENVIRONMENT

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

  2. Thin slice of a breast tumor Background on Breast Cancer http://www.jamesline.com/images/frontiers/summer2005/PartnersInCrime1.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.

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

  4. TRANSFORMED EPITHELIAL CELLS (TECs)

  5. fibroblasts myofibroblasts EXPERIMENT & MODEL DOMAIN MEMBRANE ( TECs ) ● 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. MEMBRANE - + fibroblasts ( f ) TEC ( n ) myofibroblasts ( m ) EGF (E) EGF (E) TGF-b (G) TGF-b (G) X = 0

  6. Diffusion of TECs

  7. CHEMOTAXIS : n cells move towards increasing concentration of EGF

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

  9. production of EGF by fibroblasts & myofibroblasts in -

  10. on the semi-permeable membrane

  11. ● 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.

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