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01-06-2019 | Glioblastoma | Laboratory Investigation

Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1

Authors: Wenjun Pu, Zeyad D. Nassar, Samira Khabbazi, Nan Xie, Kerrie-Ann McMahon, Robert G. Parton, Gregory J. Riggins, Jonathan M. Harris, Marie-Odile Parat

Published in: Journal of Neuro-Oncology | Issue 2/2019

Abstract

Introduction

Glioblastoma (GBM) is the most common primary brain cancer. The average survival time for the majority of patients is approximately 15 months after diagnosis. A major feature of GBM that contributes to its poor prognosis is its high invasiveness. Caveolae are plasma membrane subdomains that participate in numerous biological functions. Caveolin-1 and Caveolae Associated Protein 1 (CAVIN1), formerly termed Polymerase I and Transcript Release Factor, are both necessary for caveola formation. We hypothesized that high expression of caveola-forming proteins in GBM promotes invasiveness via modulation of the production of matrix-degrading enzymes.

Methods

The mRNA expression of caveola-forming proteins and matrix proteases in GBM samples, and survival after stratifying patients according to caveolin-1 or CAVIN1 expression, were analyzed from TCGA and REMBRANDT databases. The proteolytic profile of cell lines expressing or devoid of caveola-forming proteins was investigated using zymography and real-time qPCR. Invasion through basement membrane-like protein was investigated in vitro.

Results

Expression of both caveolin-1 and CAVIN1 was increased in GBM compared to normal samples and correlated with expression of urokinase plasminogen activator (uPA) and gelatinases. High expression of caveola-forming proteins was associated with shorter survival time. GBM cell lines capable of forming caveolae expressed more uPA and matrix metalloproteinase-2 (MMP-2) and/or -9 (MMP-9) and were more invasive than GBM cells devoid of caveola-forming proteins. Experimental manipulation of caveolin-1 or CAVIN1 expression in GBM cells recapitulated some, but not all of these features. Caveolae modulate GBM cell invasion in part via matrix protease expression.

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Title: Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1
Authors: Wenjun Pu
Zeyad D. Nassar
Samira Khabbazi
Nan Xie
Kerrie-Ann McMahon
Robert G. Parton
Gregory J. Riggins
Jonathan M. Harris
Marie-Odile Parat
Publication date: 01-06-2019
Publisher: Springer US
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Published in: Journal of Neuro-Oncology / Issue 2/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03161-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1

Abstract

Introduction

Methods

Results

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

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