Tumor Growth and Its Morphological Change Dependent On Cell-Cell and Cell-Extracellular Matrix Interactions: An off-Lattice Hybrid Discrete-Continuum (OLHDC) Model

We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of a tumor to study tumor growth and its morphological change dependent on cell-cell and cell-extracellular matrix (ECM) interactions. The continuum part of the OLHDC model describes micro-environmental components such as matrix-degrading enzymes (MDEs), nutrient or oxygen, and extracellular matrix concentrations, while the discrete portion represents individual cell behavior such as cell cycle, cell-cell and cell-ECM interactions and cell motility by the often used persistent random walk, which can be depicted by the Langevin equation. The tumor growth and its morphology were strongly affected by cell-cell adhesion and cell-ECM interaction. In the case of tumor cells with a single phenotype, if the strength of cell-cell adhesion exceeds that of cell-ECM interaction, a small circular tumor develops. When the strength of cell-cell adhesion is comparable to that of cell-ECM interaction, tumor morphology became spiky-hair shaped having higher tumor roughness. If the strength of cell-cell adhesion is weaker than that of cell-ECM interaction, overall tumor morphology became circular with less dense outer layer and more dense inner spiky-hair shape. Tumor cells with various phenotypes developed finger-like morphology with higher tumor roughness when compared to tumor cells with a single phenotype, which is an important indication that tumor cells with various phenotypes could develop invasive tumor morphology in an effective way.