Abstract
Gliomas are malignant tumors that are commonly observed in primary brain cancer. Glioma cells migrate through a dense network of normal cells in microenvironment and spread long distances within brain. In this paper we present a two-dimensional multiscale model in which a glioma cell is surrounded by normal cells and its migration is controlled by cell-mechanical components in the microenvironment via the regulation of myosin II in response to chemoattractants. Our simulation results show that the myosin II plays a key role in the deformation of the cell nucleus as the glioma cell passes through the narrow intercellular space smaller than its nuclear diameter. We also demonstrate that the coordination of biochemical and mechanical components within the cell enables a glioma cell to take the mode of amoeboid migration. This study sheds lights on the understanding of glioma infiltration through the narrow intercellular spaces and may provide a potential approach for the development of anti-invasion strategies via the injection of chemoattractants for localization.
Highlights
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumors with the survival time of approximately one year from the time of diagnosis [1]
Cell migration has two different aspects: (i) it is necessary for numerous physiological processes such as wound healing and immune responses to pathogens, and (ii) it can lead to metastasis of cancer cells
Reverse or even counterattack this critical invasion process, one ought to understand the fundamental regulation of this cell migration
Summary
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumors with the survival time of approximately one year from the time of diagnosis [1]. An aggressive invasion of glioma cells into the surrounding tissue is one of the major reasons for the treatment failure leading to the poor survival rate. This is due to the invisibility of individual migratory glioma cells even with current advanced technology and incomplete elimination of glioma cells by standard surgery [2]. Several biochemical factors such as EGF family [3] and remodeling of the extracellular matrix (ECM) may contribute to the glioma cell infiltration in brain [4]. Other types of cells such as microglia that are attracted to the tumor can secrete chemoattractants and they may contribute to the invasion of brain tumor [5]
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