Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1‐MMP, MMP‐2 and MMP‐9 in human glioblastomas

Munaut, Carine; Noël, Agnès; Hougrand, Olivier; Foidart, Jean‐Michel; Boniver, Jacques; Deprez, Manuel

doi:10.1002/ijc.11313

Cited by 143 publications

(106 citation statements)

References 36 publications

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“…It has been shown that VEGF is significantly overexpressed in GBMs (Plate et al, 1992;Shweiki et al, 1992), meningiomas, metastases and haemangioblastomas, however our data indicated up-regulation of VEGF in only 38% of tumours. Munaut et al (2003) found 2 -15-fold upregulation of VEGF mRNA in most (17 out of 20) GBMs, downregulation in two and equivalent expression in one, although the relative abundance of isoforms 165, 121, 189 and 145 varied, with 165 being the most abundant. Since our VEGF PCR primers were designed to detect all isoforms, the relative abundance of VEGF isoforms in our samples was not assessed.…”

Section: Discussionmentioning

confidence: 89%

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

et al. 2006

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Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal -epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RTpolymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in 477% tumours. Methylationspecific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.

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Section: Discussionmentioning

confidence: 89%

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

et al. 2006

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“…The finding of a positive correlation between ADAM-12 and VEGF-A 121 and VEGF-A 165 isoforms, which are proangiogenic, in all tumour samples reinforce the hypothesis of a specific role for ADAM-12 in tumour-associated angiogenic process. The potential effect of ADAM-12 on angiogenesis could occur either directly by activating some mediators implicated in angiogenesis as demonstrated for some MMPs or by inactivating angiogenesis inhibitors (Munaut et al, 2003;Maquoi et al, 2004;Noel et al, 2004). Alternatively and as suggested for other proteases, ADAMs could release proangiogenic factors trapped in the extracellular matrix by degrading its components (Werb et al, 1999).…”

Section: Discussionmentioning

confidence: 97%

“…In addition, recently, an interplay between vascular endothelial growth factor (VEGF) and metalloproteases has been reported. This new concept is supported by (1) the ability of ADAMTS-1 to bind VEGF and functionally inactivate VEGFR2 , (2) the existence of a correlation between VEGF and some MMP expression in tumours, (3) the upregulation of VEGF-A expression by the active form of membrane type-1 MMP (MT1-MMP, MMP14) (Munaut et al, 2003), (4) the reduction of VEGF expression in tumour cells by physiological inhibitor (TIMP-2) (Hajitou et al, 2001) or synthetic inhibitor of MMPs. These observations suggest the involvement of ADAM, ADAMTS and MMP members in the control of angiogenesis, a key step of metastatic dissemination.…”

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confidence: 99%

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

et al. 2006

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A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptasepolymerase chain reaction (RT -PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A 165 and VEGF-A 121 ). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression.

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“…Immunohistochemistry studies on patient samples revealed that IL-6 was localized to glioblastoma tumor cells, and IL-6 activity was detected in the cerebrospinal fluid and tumor cysts of glioblastoma patients (57). Additionally, expression of prosurvival effectors downstream of STAT-3, such as matrix metalloproteinase-9 and VEGF, was elevated in human glioblastoma tissues and implicated in tumor angiogenesis (63). It is clear from these studies that IL-6 promotes glioma development in vivo, at least in part through the action of STAT-3.…”

Section: Stat-3 Activation By Il-6 Cytokinesmentioning

confidence: 90%

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

Brantley

Benveniste

2008

Molecular Cancer Research

212

159

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Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1‐MMP, MMP‐2 and MMP‐9 in human glioblastomas

Cited by 143 publications

References 36 publications

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas

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