Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.
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.
Istituto Officina dei Materiali-National Research Council, Trieste, Italy.
Laura
L
Andolfi
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Eugenia
E
Bourkoula
Département de Chimie Moléculaire, Ingénierie et Interactions Bio Moléculaires, Université Joseph Fourier, Grenoble, France.
Elisa
E
Migliorini
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Anita
A
Palma
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Anja
A
Pucer
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Miran
M
Skrap
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Giacinto
G
Scoles
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Antonio Paolo
AP
Beltrami
Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
Daniela
D
Cesselli
Istituto Officina dei Materiali-National Research Council, Trieste, Italy; Cluster in Biomedicine, Trieste, Italy.
Marco
M
Lazzarino
D001932:Brain Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D013057:Spectrum Analysis / Q000379:methods; D014407:Tumor Cells, Cultured