title: Predicting mechanism of biphasic growth factor action on tumor growth using a multi-species model with feedback control.
abstract: A large number of growth factors and drugs are known to act in a biphasic manner: at lower concentrations they cause increased division of target cells, whereas at higher concentrations the mitogenic effect is inhibited. Often, the molecular details of the mitogenic effect of the growth factor are known, whereas the inhibitory effect is not. Hepatoctyte Growth Factor, HGF, has recently been recognized as a strong mitogen that is present in the microenvironment of solid tumors. Recent evidence suggests that HGF acts in a biphasic manner on tumor growth. We build a multi-species model of HGF action on tumor cells using different hypotheses for high dose-HGF activation of a growth inhibitor and show that the shape of the dose-response curve is directly related to the mechanism of inhibitor activation. We thus hypothesize that the shape of a dose-response curve is informative of the molecular action of the growth factor on the growth inhibitor.
authors: Department of Mathematics, University of California, Irvine, CA 92697-3875, USA ; Center for Complex Biological Systems, University of California, 2620 Biological Sciences III, Irvine, CA 92697-2280, USA.
authors: Anna
authors: A
authors: Konstorum
authors: Center for Complex Biological Systems, University of California, 2620 Biological Sciences III, Irvine, CA 92697-2280, USA ; Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA.
authors: Stephanie A
authors: SA
authors: Sprowl
authors: Center for Complex Biological Systems, University of California, 2620 Biological Sciences III, Irvine, CA 92697-2280, USA ; Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA.
authors: Marian L
authors: ML
authors: Waterman
authors: Center for Complex Biological Systems, University of California, 2620 Biological Sciences III, Irvine, CA 92697-2280, USA ; Department of Developmental and Cell Biology, University of California, 2011 Biological Sciences III, Irvine, CA 92697-2300, USA.
authors: Arthur D
authors: AD
authors: Lander
authors: Department of Mathematics, University of California, Irvine, CA 92697-3875, USA ; Center for Complex Biological Systems, University of California, 2620 Biological Sciences III, Irvine, CA 92697-2280, USA ; Department of Biomedical Engineering, University of California, 3120 Natural Sciences II, Irvine, CA 92697-2715, USA.
authors: John S
authors: JS
authors: Lowengrub
keywords: Cancer Modeling; Cell Signaling; Coupled Dynamical Modeling; Nonlinear Biological Growth Control; Stem Cells