Cellular infiltration, intra- and inter-cellular signaling and cell mechanics in tumor biology: hybrid multi-scale approaches

Yangjin Kim (May 6, 2020)

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Tumor cells interact with many players such as stromal cells (fibroblasts, myofibroblasts), immune cells (N1/N2 neutrophils, M1/M2 macrophages, NK cells, T cells), and extracellular matrix (ECM) in a tumor microenvironment in order to increase survival rates in response to multiple biomechanical and biochemical challenges. Quite often, these tumor cells exchange major regulatory molecules with other cells and use intracellular signaling pathways for regulation of cellular decision such as cell motility, proliferation, apoptosis, and necroptosis after receptor binding. For example, stem cells-like astrocytes and M1/M2 microglia communicate with glioma cells for regulation of tumor growth and cellular dispersion after surgical resection of the primary tumorcore, and one of major ECM components in brain, CSPG, was shown to play a key role in regulation of anchoring invasive glioma cells. We developed hybrid multi-scale models of cancer dynamics where intracellular components (ODEs), diffusible molecules (PDEs), and individual cells are integrated in the hybrid domain. We show how up- or down-regulation of components in these pathways in cancer cells affects the key cellular decision to infiltrate or proliferate by interacting with many players in a complex microenvironment. We take some examples in glioblastoma (brain cancer) before and after surgery, breast cancer, and metastatic circulating tumor cells (CTC).