A Multiscale Model for Hypoxia-induced Avascular Tumor Growth

We present a cell-based multiscale model for avascular tumor growth aimed at investigating the tumor morphology under hypoxia condition. At the extracellular level, the diffusion of oxygen, glucose and hydrogen ions describe the chemical dynamics involved in metabolism. At the cellular level, a Glazier-Graner-Hogeweg (GGH) model describes cellular dynamics including cell proliferation, viability and adhesion. At the subcellular level, the expression of protein p27 regulates the cell cycle. In this model each tumor cell reacts to the local environment by changing its phenotype. For example, tumor cells can adapt to the low oxygen concentration in the tissue by undergoing anaerobic metabolism. In particular, we have analyzed cancer cells can undergo quiescence (Go phase in the cell cycle) by increasing their levels of p27, which increase their survival chances in hypoxia situation. This model produces a layered structure avascular tumor that quantitatively in agreement of B16F10 melanoma in vivo experiment measurements.