Research Article A Computational Model for Investigating Tumor Apoptosis Induced by Mesenchymal Stem Cell-Derived Secretome Melisa Hendrata 1 and Janti Sudiono 2 1 Department of Mathematics, California State University, Los Angeles, CA 90032, USA 2 Department of Oral Pathology, Faculty of Dentistry, Trisakti University, Jakarta, Indonesia Correspondence should be addressed to Melisa Hendrata; mhendra@calstatela.edu Received 1 May 2016; Revised 1 August 2016; Accepted 8 August 2016 Academic Editor: Said Audi Copyright © 2016 M. Hendrata and J. Sudiono. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 efect of MSC-derived secretome in tumor growth. Te model encompasses three biological scales. At the molecular scale, a system of ordinary diferential 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 diferential equations are employed to describe the dynamics of microenvironmental chemicals concentrations. Te 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. 1. Introduction Apoptosis is a normal, genetically regulated process in which a cell undergoes a sequence of intracellular complex processes that trigger self-destruction. Cancers occur due to mutations of certain fundamental genes that disable the cells to perform apoptosis, giving rise to malignant tumor cells that grow uncontrollably. With its genetic instability, an individual tumor cell becomes a forerunner parent cell that has the potential to develop into a cluster, biologically complex tumor consisting of approximately 10 6 cells. Various cancer treatments have been explored with the ultimate goal of suppressing its growth and spreading and perhaps even eradicating cancerous cells. Recently, mes- enchymal stem cells (MSCs) have become a topic of great focus in relation to cancer. MSCs are known to secrete a broad panel of proteins including growth factors, chemokines, and cytokines, which are called secretome [1]. Growing evidence suggests that MSCs have an important role in afecting the behavior of tumor cells [2]. While some studies reported that MSCs favor tumor growth, others showed that MSCs can suppress tumorigenesis [3, 4]. In particular, it has been reported that secretome contained in conditioned media (CM) of MSCs promotes apoptosis and autophagy of cancer cells [5]. Experiments done by Sandra et al. show that secretome signifcantly induces apoptosis in HeLa cancer cells in concentration and time dependent manner [6]. From intracellular perspective, there are two well-known major signaling pathways leading to apoptosis: the intrinsic pathway centered on mitochondria and the extrinsic pathway initiated by death receptors called Tumor Necrosis Factor (TNF). Tere is now evidence showing that these two path- ways are connected and afect one another [7, 8]. Moreover, recent research has also revealed the third pathway, called the perforin pathway, which involves T-cell mediated cytotoxicity and is induced by granzyme B protein. Perforin pathway is also connected to the intrinsic pathway and all three pathways eventually converge into the activation of caspase 3 protein leading to cell death, chromatin condensation, chromosome Hindawi Publishing Corporation Computational and Mathematical Methods in Medicine Volume 2016, Article ID 4910603, 17 pages http://dx.doi.org/10.1155/2016/4910603