Decreased expression of heparanase in glioblastoma multiforme

Ueno, Yushi; Yamamoto, Masaaki; Vlodavsky, Israël; Pecker, Iris; Ohshima, Kohichi; Fukushima, Takeo

doi:10.3171/jns.2005.102.3.0513

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…The present data are also consistent with previous reports that describe a positive correlation between heparanase expression and tumor progression in cases of bladder, colon, pancreatic, hepatocellular, oral, gastric, esophageal, cervical, non–small cell lung, and head and neck cancers (13–22) . In contrast, it has also been reported that the expression of heparanase is downregulated in glioblastoma multiforme and in prostate cancer (23,24) . These findings suggest, however, that heparanase expression may contribute to the progression of the majority of malignant solid tumors.…”

Section: Discussionsupporting

confidence: 93%

Heparanase expression in both normal endometrium and endometrial cancer

Kodama

Kusumoto

Seki

et al. 2006

Int J Gynecol Cancer

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The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P= .012 and P= .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P= .0003) and high FIGO grade (P= .004) and with cancers showing either deep myometrial invasion (P= .023), lymph node metastasis (P= .006), lymphvascular space involvement (P= .048), or positive peritoneal cytology (P= .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P= .004 and P= .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.

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Section: Discussionsupporting

confidence: 93%

Heparanase expression in both normal endometrium and endometrial cancer

Kodama

Kusumoto

Seki

et al. 2006

Int J Gynecol Cancer

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“…Moderately elevated expression of HPSE in the glioma cell line U87 resulted in increased invasion in vitro and tumor size after xenografting, but further increases in HPSE levels resulted in reduced in vitro proliferation and in vivo tumor growth [119]. In another report, HPSE was not found in human GBM, and after injection of U87 into the immunocompromised mouse brain, HPSE expression was lost [120]. When comparing HPSE expression across oligodendroglioma, anaplastic astrocytoma, and GBM, the authors did not find a correlation between HPSE and WHO grade, although the expression level was higher than in normal brain [121].…”

Section: Glioma-associated Changes In the Ecm Include Alterations In mentioning

confidence: 99%

Heparan sulfate in the regulation of neural differentiation and glioma development

2014

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Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

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“…In multiple myeloma, a number of oncogenic functions for HPSE have been identified including direct effects on tumor cells and indirect effects on tumor-associated endothelial cells (10,23,23–25). In the brain, HPSE has been implicated in metastatic tumor cell invasion and medulloblastoma cell signaling (26–28), but its role in GBM is less established (29,30) although recent studies suggest its importance in tumor progression (31). …”

Section: Introductionmentioning

confidence: 99%

Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion

Tran

Wade

McKinney

et al. 2017

Molecular Cancer Research

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Glioblastoma (GBM) is the most common primary malignant brain tumor of adults and confers a poor prognosis due, in part, to diffuse invasion of tumor cells. Heparan sulfate (HS) glycosaminoglycans, present on the cell surface and in the extracellular matrix, regulate cell signaling pathways and cell-microenvironment interactions. In GBM, the expression of HS glycosaminoglycans and the enzymes that regulate their function are altered but the actual HS content and structure are unknown. However, inhibition of HS glycosaminoglycan function is emerging as a promising therapeutic strategy for some cancers. In this study, we use liquid chromatography-mass spectrometry (LC/MS) analysis to demonstrate differences in HS disaccharide content and structure across four patient-derived tumorsphere lines (GBM1, 5, 6, 43) and between two murine tumorsphere lines derived from murine GBM with enrichment of mesenchymal and proneural gene expression (mMES and mPN, respectively) markers. In GBM, the heterogeneous HS content and structure across patient-derived tumorsphere lines suggested diverse functions in the GBM tumor microenvironment (TME). In GBM5 and mPN, elevated expression of sulfatase 2 (SULF2), an extracellular enzyme that alters ligand binding to HS, was associated with low trisulfated HS disaccharides, a substrate of SULF2. In contrast, other primary tumorsphere lines had elevated expression of the HS-modifying enzyme heparanase (HPSE). Using gene editing strategies to inhibit HPSE a role for HPSE in promoting tumor cell adhesion and invasion was identified. These studies characterize the heterogeneity in HS glycosaminoglycan content and structure across GBM and reveal their role in tumor cell invasion.

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Decreased expression of heparanase in glioblastoma multiforme

Abstract: These results indicate that the expression of heparanase was downregulated in GBM in vivo, which rarely metastasizes to distant organs outside the central nervous system. Heparanase is not implicated in the invasiveness of GBM to surrounding healthy brain tissue in vivo.

Cited by 13 publications

References 33 publications

Heparanase expression in both normal endometrium and endometrial cancer

Heparanase expression in both normal endometrium and endometrial cancer

Heparan sulfate in the regulation of neural differentiation and glioma development

Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion

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