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

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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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Fig. 1

Data were extracted from Project Betastasis web platform (http://www.betastasis.com)

Fig. 2

Data were extracted from Project Betastasis web platform (http://www.betastasis.com)

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Funding

This study was funded by the School of Pharmacy, University of Queensland. Zeyad Nassar is currently supported by a National Health and Medical Research Center Early Career Fellowship (1138648).

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Authors and Affiliations

  1. PACE, University of Queensland School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia

    Wenjun Pu, Samira Khabbazi, Nan Xie & Marie-Odile Parat

  2. School of Medicine and Freemasons Foundation Centre for Men’s Health, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia

    Zeyad D. Nassar

  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

    Kerrie-Ann McMahon & Robert G. Parton

  4. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21213, USA

    Gregory J. Riggins

  5. Institute of Health Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

    Jonathan M. Harris

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  1. Wenjun Pu
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Correspondence to Marie-Odile Parat.

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Pu, W., Nassar, Z.D., Khabbazi, S. et al. Correlation of the invasive potential of glioblastoma and expression of caveola-forming proteins caveolin-1 and CAVIN1. J Neurooncol 143, 207–220 (2019). https://doi.org/10.1007/s11060-019-03161-8

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