The role of myosin II in glioma invasion: A mathematical model

PLoS One. 2017 Feb 6;12(2):e0171312. doi: 10.1371/journal.pone.0171312. eCollection 2017.

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.

MeSH terms

  • Actins / metabolism
  • Algorithms
  • Animals
  • Biomechanical Phenomena
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemotactic Factors / metabolism
  • Diffusion
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Models, Theoretical*
  • Myosin Type II / metabolism*
  • Neoplasm Invasiveness
  • Rats

Substances

  • Actins
  • Chemotactic Factors
  • Myosin Type II

Grants and funding

This research (Y. Kim) was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A01058702) and the faculty research fund of Konkuk University in 2014. Lee’s work was supported by the National Institute for Mathematical Sciences (NIMS) grant funded by Korea government (A21300000). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.