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J Neurooncol. 2019 Jun;143(2):207-220. doi: 10.1007/s11060-019-03161-8. Epub 2019 Apr 4.

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

Author information

1
PACE, University of Queensland School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
2
School of Medicine and Freemasons Foundation Centre for Men's Health, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
3
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
4
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21213, USA.
5
Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
6
PACE, University of Queensland School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia. m.parat@uq.edu.au.

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.

KEYWORDS:

Caveolae; Invasion; MMP2; MMP9; uPA

PMID:
30949900
DOI:
10.1007/s11060-019-03161-8

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