title: Collective behavior of brain tumor cells: the role of hypoxia.
abstract: We consider emergent collective behavior of a multicellular biological system. Specifically, we investigate the role of hypoxia (lack of oxygen) in migration of brain tumor cells. We performed two series of cell migration experiments. In the first set of experiments, cell migration away from a tumor spheroid was investigated. The second set of experiments was performed in a typical wound-healing geometry: Cells were placed on a substrate, a scratch was made, and cell migration into the gap was investigated. Experiments show a surprising result: Cells under normal and hypoxic conditions have migrated the same distance in the "spheroid" experiment, while in the "scratch" experiment cells under normal conditions migrated much faster than under hypoxic conditions. To explain this paradox, we formulate a discrete stochastic model for cell dynamics. The theoretical model explains our experimental observations and suggests that hypoxia decreases both the motility of cells and the strength of cell-cell adhesion. The theoretical predictions were further verified in independent experiments.
authors.affiliation: Department of Physics, Oakland University, Rochester, Michigan 48309, USA.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Khain
authors.forename: Mark
authors.initials: M
authors.lastname: Katakowski
authors.forename: Scott
authors.initials: S
authors.lastname: Hopkins
authors.forename: Alexandra
authors.initials: A
authors.lastname: Szalad
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zheng
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004058:Diffusion; D005910:Glioma / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D008954:Models, Biological; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D010100:Oxygen