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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.

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PACE, University of Queensland School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
School of Medicine and Freemasons Foundation Centre for Men's Health, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21213, USA.
Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
PACE, University of Queensland School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.



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.


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.


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.


Caveolae; Invasion; MMP2; MMP9; uPA


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