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

AI Article Synopsis

  • Glioblastoma (GBM) is a highly invasive brain cancer with an average survival time of about 15 months after diagnosis and is linked to the expression of caveola-forming proteins.
  • Research indicates that high levels of caveolin-1 and CAVIN1 in GBM are associated with increased expression of matrix-degrading enzymes, correlating with shorter patient survival.
  • Experimental results show GBM cells with caveolae are more invasive and produce higher levels of key proteins like uPA and MMPs compared to those without these proteins, suggesting that caveolae play a significant role in promoting GBM invasion.

Article 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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Source
http://dx.doi.org/10.1007/s11060-019-03161-8DOI Listing

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