Program
| CTB6b | |
|---|---|
| Mathilde Badoual | |
| Paris 7 University | |
| Title | A "go or grow" model based on cell interactions in brain tumours |
| Abstract | Glioblastomas are malignant brain tumours associated with poor prognosis, due to the capacity of glioma cells to invade normal brain tissue.
During their migration, cancerous astrocytes interact with other cancerous cells (homotype interactions) as well as with normal motionless astrocytes (heterotype interactions), in particular through gap junctions. These interactions appear to strongly influence the migration of glioma cells. We have developped a cellular automaton where the strength of each type of interaction is ajustable, in order to describe the migration of glioma cells [1,2,3]. From this automaton, we were able to derive a macroscopic diffusion equation, where the diffusion coefficient is original compared to other classical models [4]. First, the diffusion coefficient is nonlinear as it depends on the cell density. Second, it depends on the two parameters measuring the strength of homotype and heterotype interactions, as well as on the number of normal astrocytes coupled to a cancerous astrocyte, through heterotype gap junctions.
We show that the inhibition of homotype gap junctions leads to the increase of cell migration, whereas when both homotype and heterotype gap junctions are involved, their inhibition leads to a reduction of migration. This result is in agreement with experimental data [5]. Our model also accounts for the variability of the expression of connexin 43 (the major junctional protein in astrocytes) through different tumours. We suggest that the various migrating behaviours observed among cells in a tumour correspond to different expressions of connexin 43 and we propose a model for the "go or grow" hypothesis, based on a differential connexin 43 expression.
[1] Aubert M, Badoual M, Fereol S, Christov C and Grammaticos B, 2006, A cellular automaton model for the migration of glioma cells, Phys. Biol., 3, 93. [2] Aubert M, Badoual M, Christov C and Grammaticos B, 2008, A model for glioma cell migration on collagen and astrocytes, J. R. Soc. Interface, 5, 75. [3] Deroulers C, Aubert M, Badoual M, Grammaticos B., Modeling tumor cell migration: From microscopic to macroscopic models, 2009, Phys Rev E Stat Nonlin Soft Matter Phys. 79, 031917. [4] Tracqui P, Cruywagen GC, Woodward DE, Bartoo GT, Murray JD and Alvord EC Jr, A mathematical model of glioma growth: the effect of chemotherapy on spatio-temporal growth, Cell Prolif, 1995, 28, 17-31. [5] Oliveira R, Christov C, Guillamo J S, de Bouard S, Palfi S, Venance L, Tardy M and Peschanski M, 2005, Contribution of gap junctional communication between tumor cells and astroglia to the invasion of the brain parenchyma by human glioblastomas BMC Cell Biol., 6, 7. |
| Coauthors | Christophe Deroulers, Marine Aubert and Basile Grammaticos |
| Location | Woodward 6 |