Thrombospondin-1 Is Downregulated by Anoxia and Suppresses Tumorigenicity of Human Glioblastoma Cells

Tenan, Mirna; Fulci, Giulia; Albertoni, Michele; Diserens, Annie‐Claire; Hamou, Marie‐France; Atifi-Borel, Michèle El; Feige, Jean‐Jacques; Pepper, Michael Sean; Meir, Erwin G. Van

doi:10.1084/jem.191.10.1789

Cited by 98 publications

(68 citation statements)

References 36 publications

(52 reference statements)

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“…A decline in chemokine (C-X-C motif), hypothelical protein, and insulin-induced gene 1 detected in this study was consistent with a report by Zheng et al (2003). Recently, it has been shown that thrombospondin 1, a natural inhibitor of angiogenesis, is downregulated in malignant glioma cells by anoxia (Tenan et al, 2000). Therefore, inhibition of thrombospondin 1 might be due to hypoxic stress following exposure of tumor cells to As 2 O 3 .…”

Section: Downregulated Genes In U373-mg Cells Treated With As 2 Osupporting

confidence: 81%

Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3

et al. 2004

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Arsenic trioxide (As 2 O 3 ) has shown considerable efficacy in treating hematological malignancies with induction of programmed cell death (PCD) type I, apoptosis. However, the mechanisms underlying the antitumor effect of As 2 O 3 on solid tumors are poorly defined. Previously, we reported that As 2 O 3 induced autophagic cell death (PCD type II) but not apoptosis in human malignant glioma cell lines. The purpose of this study was to elucidate the molecular pathway leading to autophagic cell death. In this study, we demonstrated that the cell death was accompanied by involvement of autophagy-specific marker, microtubule-associated protein light chain 3 (LC3), and damage of mitochondrial membrane integrity, but not by caspase activation. Analysis by cDNA microarray, RT-PCR, and Western blot showed that cell death members of Bcl-2 family, Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) and its homologue BNIP3-like (BNIP3L), were upregulated in As 2 O 3 -induced autophagic cell death. Exogenous expression of BNIP3, but not BNIP3L, induced autophagic cell death in malignant glioma cells without As 2 O 3 treatment. When upregulation of BNIP3 induced by As 2 O 3 was suppressed by a dominant-negative effect of the transmembranedeleted BNIP3 (BNIP3DTM), autophagic cell death was inhibited. In contrast, BNIP3 transfection augmented As 2 O 3 -induced autophagic cell death. These results suggest that BNIP3 plays a central role in As 2 O 3 -induced autophagic cell death in malignant glioma cells. This study adds a new concept to characterize the pathways by which As 2 O 3 acts to induce autophagic cell death in malignant glioma cells. Oncogene (2005) 24, 980-991.

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Section: Downregulated Genes In U373-mg Cells Treated With As 2 Osupporting

confidence: 81%

Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3

et al. 2004

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“…In hepatocellular carcinoma there is a significant relationship between tumour TSP1 levels and venous invasion even in patients with high and low tumour VEGF levels (Poon et al, 2004). It is thought that TSP1 expression in brain tumours is influenced by several factors including hypoxia, cell density (in vitro) and cell type (Tenan et al, 2000;Kawataki et al, 2000;Laderoute et al, 2000;Filleur et al, 2001;Naganuma et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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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“…Our knowledge of the mechanism of action of TSRs on endothelium comes from the study of TSP-1. Overexpression of TSP-1 or its TSRs has been shown to inhibit tumor growth and angiogenesis in a variety of malignancies (Tolsma et al, 1993;Weinstat-Saslow et al, 1994;Volpert et al, 1998;Bleuel et al, 1999;Streit et al, 1999;Tenan et al, 2000). TSP-1 directly interacts with endothelial cells through binding of its TSRs to CD36, a cell surface receptor.…”

Section: Discussionmentioning

confidence: 99%

Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

et al. 2005

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Thrombospondin-1 Is Downregulated by Anoxia and Suppresses Tumorigenicity of Human Glioblastoma Cells

Cited by 98 publications

References 36 publications

Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3

Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3

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

Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

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