Correlation of thrombospondin‐1 and transforming growth factor‐β expression with malignancy of glioma

Kawataki, Tomoyuki; Naganuma, Hirofumi; Sasaki, Atsushi; Yoshikawa, Hideji; Tasaka, Kachio; Nukui, Hideaki

doi:10.1046/j.1440-1789.2000.00327.x

Cited by 61 publications

(52 citation statements)

References 48 publications

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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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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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“…Human T98G, A172 and YMG5 glioblastoma cell lines (T98G and A172 cell lines; obtained from the Japanese Cancer Research Resources Bank, Tokyo, Japan) were selected for our study because they secrete significant amounts of TSP-1 7 and can activate TGF-␤ by themselves. 8,9 YMG5 glioblastoma cell line was established in our laboratory.…”

Section: Cell Culturementioning

confidence: 99%

“…The T98G cell line was selected for our study because it expresses TSP-1 messenger ribonucleic acid (mRNA) but not TSP-2 mRNA and secretes a significant amount of TSP-1 protein. 7 We hypothesized that this would lead to decreased expression of TSP-1 and consequently affect the tumor cell motility. We also treated T98G-G7 and TSP-1-secreting A172 and YMG5 glioblastoma cells with a synthetic peptide that included 3 sequences of the adhesion site in the TSP-1 molecule to investigate whether similar effects on cell motility could be obtained to those induced by antisense-transfected cells.…”

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confidence: 99%

“…T98G and A172 cells secrete a high amount of TSP-1 among malignant glioma cell lines, whereas the YMG5 cells belong to a group that secretes a low amount of TSP-1. 7 The glioma cells were cultured in RPMI1640 medium supplemented with 10% fetal bovine serum (FBS), 2 mM glutamine and 100 g/ml kanamycin and subcultured every 3-5 days. …”

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confidence: 99%

“…6 Our recent study showed that malignant glioma cells secreted a significant amount of TSP-1 and its level of expression seemed to correlate with the degree of malignancy. 7 The involvement of TSP-1 expression in the motility of glioma cells, however, is not well known. This issue is important because prominent invasiveness of tumor cells into surrounding brain tissue is 1 of the malignant characteristics of most glioma types.…”

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Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

et al. 2001

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Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-␤. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisensetransfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a doserelated manner. Maximum inhibition of migration was achieved by 100 g/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells. © 2001 Wiley-Liss, Inc. Key words: thrombospondin-1; glioma; glioblastoma; cell motility; invasionThrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-␤ (TGF-␤). 1,2 TSP-1 is a member of a family of structurally related proteins encoded by different genes, which includes 4 recently identified members designated TSP-2, TSP-3, TSP-4 and TSP-5/cartilage oligomeric matrix protein. 3 TSP-1 and TSP-2 have similar overall structures, which differ from those of TSP-3, TSP-4 and TSP-5. 3 TSP-1 is secreted by platelets and synthesized by many cell types, including endothelial and tumor cells. 1,2 TSP-1 consists of multiple domains, including an amino-terminal heparin-binding domain, a procollagen-like domain, 3 type I (properdin-like) repeats, 3 type II (epidermal growth factor-like) repeats, 7 type III (calcium-binding) repeats and a carboxy-terminal cellbinding domain that lacks homology to other proteins. Eleven sites for adhesion have been identified. 1 A potential role for TSP-1 in cancer is suggested by its regulated expression in many normal and tumor cells and by its ability to modulate the adhesion and motility of many types of tumor cells in vitro. 4 Adhesion molecules are potentia...

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Darts in the Dark Cure Animal, but Not Human, Brain Tumors

Fathallah‐Shaykh¹

2002

Arch Neurol

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Correlation of thrombospondin‐1 and transforming growth factor‐β expression with malignancy of glioma

Cited by 61 publications

References 48 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

Antisense‐mediated reduction in thrombospondin‐1 expression reduces cell motility in malignant glioma cells

Darts in the Dark Cure Animal, but Not Human, Brain Tumors

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