Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy

PLoS One. 2014 Nov 12;9(11):e112582. doi: 10.1371/journal.pone.0112582. eCollection 2014.

Abstract

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / pathology*
  • Cell Adhesion / physiology*
  • Cell Movement / physiology
  • Glioma / pathology*
  • Humans
  • Microscopy, Atomic Force / methods
  • Neoplasm Invasiveness / pathology*
  • Neoplastic Stem Cells / pathology*
  • Spectrum Analysis / methods
  • Tumor Cells, Cultured

Grants and funding

This work was supported by: European Union Seventh Framework Programme (FP7/2007-2013) n°270483 FP7 ICT - FOCUS Single Molecule Activation and Computing; FIRB Accordi di programma 2011; title: “FIERCE – FInd nEw moleculaR and CEllular targets against cancer”, Pr. RBAP11Z4Z9. 2012-2014; FIRB accordi di programma 2011 pr. RBAP11ETKA_007 “Nanotechnological approaches for tumor theragnostic”; Programma per la Cooperazione Transfrontaliera Italia-Slovenia 2007-2013, title: “Identificazione di nuovi marcatori di cellule staminali tumorali a scopo diagnostico e terapeutico”; AIRC 5 per mille Special program 2011, Pr. 12214, title: “Application of Advanced Nanotechnology in the Development of Cancer Diagnostics Tools”; Project ERC- 7FP SP 2 IDEAS QUIDPROQUO G.A. n. 269051, title: “Molecular nanotechnology for life science applications: quantitative interactomics for diagnostics, proteomics and quantitative oncology”. The funders had no role in the study, data collection and analysis, decision to publish, or preparation of the manuscript.