<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><bold>Introduction.</bold> CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential and differentiation of these stem cells is associated with CD133 expression and with cathepsin proteases (Cats).<bold>Materials and methods.</bold> The invasiveness of normal NNSC, GBM/CD133+ cell lines and GBM spheroids was evaluated in 3D collagen, as well as of U87-MG and normal astrocytes (NHA) grown in monolayers in 2D Matrigel. Expression of Cats B, L and S was measured at mRNA and activity levels and their relation to invasiveness, to CD133 mRNA in 26 gliomas, and to the survival of these patients.<bold>Results.</bold> The average yield of CD133+ cells from GBM samples was 9.6%. Survival of patients with higher CD133 mRNA expression was significantly shorter (p&lt; 0.005). Invasion, associated with proteolytic degradation of matrix, was higher in normal stem cells and GBM spheroids and cells than in isolated GBM CD133+ cells. In glioma samples, there was no correlation between CD133 mRNA expression and Cat mRNAs, but there was an inverse correlation with Cat activities.<bold>Conclusions.</bold> The study confirms CD133 as a prognostic marker for the survival of GBM patients. We demonstrated that NNSC have higher invasion potential and invade the collagen matrix in a mode different from that of GBM, initiating stem cell spheres. This result could have implications for the design of new therapeutics, including protease inhibitors that specifically target invasive tumour stem cells. Increased activity of cathepsins in CD133- cells suggests their role in the invasive behaviour of GBM.</abstract>

Introduction. CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential and differentiation of these stem cells is associated with CD133 expression and with cathepsin proteases (Cats).Materials and methods. The invasiveness of normal NNSC, GBM/CD133+ cell lines and GBM spheroids was evaluated in 3D collagen, as well as of U87-MG and normal astrocytes (NHA) grown in monolayers in 2D Matrigel. Expression of Cats B, L and S was measured at mRNA and activity levels and their relation to invasiveness, to CD133 mRNA in 26 gliomas, and to the survival of these patients.Results. The average yield of CD133+ cells from GBM samples was 9.6%. Survival of patients with higher CD133 mRNA expression was significantly shorter (p< 0.005). Invasion, associated with proteolytic degradation of matrix, was higher in normal stem cells and GBM spheroids and cells than in isolated GBM CD133+ cells. In glioma samples, there was no correlation between CD133 mRNA expression and Cat mRNAs, but there was an inverse correlation with Cat activities.Conclusions. The study confirms CD133 as a prognostic marker for the survival of GBM patients. We demonstrated that NNSC have higher invasion potential and invade the collagen matrix in a mode different from that of GBM, initiating stem cell spheres. This result could have implications for the design of new therapeutics, including protease inhibitors that specifically target invasive tumour stem cells. Increased activity of cathepsins in CD133- cells suggests their role in the invasive behaviour of GBM.

CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsins' expression in glioblastoma derived spheroids

Department of Neurosurgery, University Medical Centre, Ljubljana, Slovenia

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia

Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany

Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

Radiology and Oncology

Introduction. CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential...

CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsins' expression in glioblastoma derived spheroids

Pubblicato online: 03 giu 2011

Pagine: 102 - 115

DOI: https://doi.org/10.2478/v10019-011-0015-6

Parole chiave
CD133/prominin1, cysteine cathepsins, glioblastoma, glioma stem cells, invasion, neural stem cells

This content is open access.

CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsins' expression in glioblastoma derived spheroids

Pubblicato online: 03 giu 2011

Pagine: 102 - 115

DOI: https://doi.org/10.2478/v10019-011-0015-6

Parole chiaveCD133/prominin1, cysteine cathepsins, glioblastoma, glioma stem cells, invasion, neural stem cells

This content is open access.

Parole chiave
CD133/prominin1, cysteine cathepsins, glioblastoma, glioma stem cells, invasion, neural stem cells