Investigation of the Migration/Proliferation Dichotomy and its Impact on Avascular Glioma Invasion

Abstract

Abstract. Gliomas are highly invasive brain tumors that exhibit high and spatially heterogeneous cell proliferation and motility rates. The interplay of proliferation and migration dynamics plays an important role in the invasion of these malignant tumors. We analyze the regulation of proliferation and migration processes with a lattice-gas cellular automaton (LGCA). We study and characterize the influence of the migration/proliferation dichotomy (also known as the "Go-or-Grow" mechanism) on avascular glioma invasion, in terms of invasion speed and width of the infiltration zone. We show that the invasive behavior of the (macroscopic) tumor colony is a highly complex phenomenon that cannot be extrapolated by the sole knowledge of the (microscopic) individual cell phenotype.

The biology and mathematical modelling of glioma invasion: a review

“…However, incorporating the 'Go-or-Grow' mechanism in a corresponding LGCA model allows to explain fast glioma recurrence. In addition, a discrete stochastic model was used to characterize and quantify the invasive glioma front width and speed [28]. Model simulations reveal that the 'Go-or-Grow' mechanism results in a nonlinear temporal evolution of the invasion front speed and a timedivergent infiltration zone.…”

“…Mathematical models and computational approaches have become increasingly abundant in cancer research to study tumour dynamics and responses to treatment modalities such as chemo-and radiotherapy [17][18][19][20]. Mathematical modelling provides a useful theoretical framework to perform in silico experiments, as well as to evaluate assumptions and make predictions that can be experimentally tested [21][22][23][24][25][26][27][28][29][30][31][32]. In the last two decades, several mathematical models have been developed to investigate key mechanisms governing glioma growth and invasion [23,[33][34][35].…”

A Multiscale Modeling Approach to Glioma Invasion with Therapy

“…Concerning the treatment we use the idea of reducing tumor cell migration by inhibiting the binding of cell surface receptors to the tissue fibers in the peritumoral region (see e.g., [11,23] and the references therein), hence also rendering the cancer cells more sensitive against radiotherapy, in view of the go-or-grow hypothesis stating that the tumor cells can either migrate or proliferate [9,25,23,29]. On the other hand, however, the receptor binding inhibition can also impair cell proliferation, as the latter is known to be influenced by cell-matrix (and cell-cell) adhesion [14,27,32,40,45,63]; hence, the balance between increasing proliferation through stopping migration and reducing mitotic activity through inhibiting adhesion will be the driving factor for enhancing radiosensitivity.…”

Simulating tissue mechanics with agent-based models: concepts, perspectives and some novel results

“…In the simulations of fluids, the velocity channels represented particle collisions. Deutsch and co-workers extended the framework to model growth and migration of cells in multi-cellular environments [46,69,99,100]. In our description we very closely follow the line of argument presented by Hatzikirou and Deutsch in [101], which we consider as an excellent presentation addressing the underlying concepts of LGCA for modeling of tissue organization and growth.…”

“…Recent work by Deutsch and co-workers attempt to infer the largescale behavior of LGCA for multicellular organization to better understand the large scale effect of the microscopic (cell scale) LGCA rules [99,100,102].…”