title: A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome.
abstract: Apoptosis is a programmed cell death that occurs naturally in physiological and pathological conditions. Defective apoptosis can trigger the development and progression of cancer. Experiments suggest the ability of secretome derived from mesenchymal stem cells (MSC) to induce apoptosis in cancer cells. We develop a hybrid discrete-continuous multiscale model to further investigate the effect of MSC-derived secretome in tumor growth. The model encompasses three biological scales. At the molecular scale, a system of ordinary differential equations regulate the expression of proteins involved in apoptosis signaling pathways. At the cellular scale, discrete equations control cellular migration, phenotypic switching, and proliferation. At the extracellular scale, a system of partial differential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. The simulation is able to produce both avascular tumor growth rate and phenotypic patterns as observed in the experiments. In addition, we obtain good quantitative agreements with the experimental data on the apoptosis of HeLa cancer cells treated with MSC-derived secretome. We use this model to predict the growth of avascular tumor under various secretome concentrations over time.
authors.affiliation: Department of Mathematics, California State University, Los Angeles, CA 90032, USA.
authors.forename: Melisa
authors.identifier: 0000-0002-1274-7895
authors.initials: M
authors.lastname: Hendrata
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Trisakti University, Jakarta, Indonesia.
authors.forename: Janti
authors.initials: J
authors.lastname: Sudiono
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D004058:Diffusion; D004798:Enzymes / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D015233:Models, Statistical; D009336:Necrosis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054353:Perforin / Q000378:metabolism; D010641:Phenotype; D020543:Proteome; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004798:Enzymes; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin