Development of a three-dimensional multiscale agent-based tumor model: simulating gene-protein interaction profiles, cell phenotypes and multicellular patterns in brain cancer.
Experimental evidence suggests that epidermal growth factor receptor (EGFR)-mediated activation of the signaling protein phospholipase Cgamma plays a critical role in a cancer cell's phenotypic decision to either proliferate or to migrate at a given point in time. Here, we present a novel three-dimensional multiscale agent-based model to simulate this cellular decision process in the context of a virtual brain tumor. Each tumor cell is equipped with an EGFR gene-protein interaction network module that also connects to a simplified cell cycle description. The simulation results show that over time proliferative and migratory cell populations not only oscillate but also directly impact the spatio-temporal expansion patterns of the entire cancer system. The percentage change in the concentration of the sub-cellular interaction network's molecular components fluctuates, and, for the 'proliferation-to-migration' switch we find that the phenotype triggering molecular profile to some degree varies as the tumor system grows and the microenvironment changes. We discuss potential implications of these findings for experimental and clinical cancer research.
Zhang
Le
L
Complex Biosystems Modeling Laboratory, Harvard-MIT HST Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital-East, 2301, Bldg. 149, 13th Street, Charlestown, MA 02129, USA.
Athale
Chaitanya A
CA
Deisboeck
Thomas S
TS
D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002633:Chemotaxis; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction
D009363:Neoplasm Proteins; D066246:ErbB Receptors