An In Silico Cell Signaling-Based Approach for Exploring the Activities Involved in Pre-Metastasis and Metastasis

Abstract

SUMMARYIn order to understand, identify and explore the activities involved in metastasis, as well as possible control points, in this work we model and simulate the sequential steps that a cell must follow from its transformation to metastasis, using the Cellulat bioinformatics tool, an in silico experimentation environment that complements and guides in vitro experimentation concerning intra and intercellular signaling networks. KEYWORDSMetastasis; Cancer cells; In silico experiments; Cellulat bioinformatics tool. BODYMetastasis is the clinical term for the process by which tumor cells leave a primary cancer tumor to transfer to different organs. The metastasis is considered to be the true killer in cancer patients, since usually when this process is triggered, it inevitably leads to death. To prevent the spreading of cancer, the most important is to avoid the metastasis of the primary tumor, as well as to find markers that allow early identification of the presence of a primary tumor [1]. Features that promote metastasis -i.e., sustained proliferation, replicative immortality, and evasion of growth suppression -allow cancer cells to grow uncontrollably in a tumor large enough to invade neighboring tissues. The ability of cells to resist cell death and prevent their destruction caused by the immune system response, allow them to survive on their way to metastasis.The intrinsic complexity of biological systems and phenomena -such as protein-protein interaction, protein-ligand docking and protein folding, just to mention a few examples -has required the development of a wide range of computational tools dedicated to the modeling and simulation of them, so that these computational approaches -also known as computer simulation or in silico experimentation -can complement, corroborate and enrich both the advances in theoretical and experimental research in the study of such systems. Regarding cancer research, in the last years it has found valuable support in a wide range of modeling and simulation approaches, which cover a wide spectrum ranging from mathematical models -e.g., continuous models [2][3][4] [17]. These approaches have allowed the in silico experimentation in cancer at the cellular, system and patient level.In order to understand, identify and explore the activities involved in metastasis, as well as possible control points, in this work we model and simulate the sequential steps that a cell must follow from its transformation to metastasis.We simulate and explore the complex interaction patterns of signaling pathways involved in pre-metastasis and metastasis using the Cellulat bioinformatics tool (http://bioinformatics.cua.uam.mx/node/10) [18,19], a computational simulation tool developed by us and inspired by Biochemical Tuple Spaces for Self-Organizing Coordination model (BTSSOC) [20]. The main idea behind the Cellulat bioinformatics tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation concerning intra and intercellular signaling networks.C...