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Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells.

Tenan M, Fulci G, Albertoni M, Diserens AC, Hamou MF, El Atifi-Borel M, Feige JJ, Pepper MS, Van Meir EG - J. Exp. Med. (2000)

Bottom Line: Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells.This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors.This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Tumor Biology and Genetics, Neurosurgery Department, University Hospital (CHUV), 1011 Lausanne, Switzerland.

ABSTRACT
Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

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Immunoprecipitation of cellular p53 and TSP-1. Clones wt4 and wt11, derived from parental LN-Z308 cells, contain a wt TP53 gene under a tetracycline-regulated promoter (+, with tet; −, without tet). In the wt1 clone, p53 is not induced upon tetracycline removal and served as a negative control 13. The antibodies used were A6.1 (GIBCO BRL) for TSP-1 and G59-13 (PharMingen) for p53. Similar results were obtained with anti-TSP-1 antibody A4.1 (GIBCO BRL) (not shown).
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Figure 1: Immunoprecipitation of cellular p53 and TSP-1. Clones wt4 and wt11, derived from parental LN-Z308 cells, contain a wt TP53 gene under a tetracycline-regulated promoter (+, with tet; −, without tet). In the wt1 clone, p53 is not induced upon tetracycline removal and served as a negative control 13. The antibodies used were A6.1 (GIBCO BRL) for TSP-1 and G59-13 (PharMingen) for p53. Similar results were obtained with anti-TSP-1 antibody A4.1 (GIBCO BRL) (not shown).

Mentions: To first establish whether TSP-1 might be related to GD-AIF and mediate p53 control on angiogenesis, we examined whether p53 could regulate TSP-1 expression in glioblastoma cells. TSP-1 expression was analyzed in LN-Z308 glioblastoma cells, where p53 can be regulated by tetracycline 13. Cellular TSP-1 levels were measured in two clones conditionally inducible for p53 (wt4, wt11) in the presence (no induction) or absence (p53 induction) of tetracycline and in a control clone not inducible for p53 (wt1). The amounts of immunoprecipitated TSP-1 protein did not differ upon wt p53 induction in both wt4 and wt11 clones (Fig. 1). Moreover, Northern blotting on five glioblastoma cell lines with wt (U87MG, D247MG) or mutant (LN-229, LN-319, LN-Z308) TP53 alleles 30 did not show any correlation between TSP-1 mRNA expression and TP53 gene status (data not shown).


Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells.

Tenan M, Fulci G, Albertoni M, Diserens AC, Hamou MF, El Atifi-Borel M, Feige JJ, Pepper MS, Van Meir EG - J. Exp. Med. (2000)

Immunoprecipitation of cellular p53 and TSP-1. Clones wt4 and wt11, derived from parental LN-Z308 cells, contain a wt TP53 gene under a tetracycline-regulated promoter (+, with tet; −, without tet). In the wt1 clone, p53 is not induced upon tetracycline removal and served as a negative control 13. The antibodies used were A6.1 (GIBCO BRL) for TSP-1 and G59-13 (PharMingen) for p53. Similar results were obtained with anti-TSP-1 antibody A4.1 (GIBCO BRL) (not shown).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193158&req=5

Figure 1: Immunoprecipitation of cellular p53 and TSP-1. Clones wt4 and wt11, derived from parental LN-Z308 cells, contain a wt TP53 gene under a tetracycline-regulated promoter (+, with tet; −, without tet). In the wt1 clone, p53 is not induced upon tetracycline removal and served as a negative control 13. The antibodies used were A6.1 (GIBCO BRL) for TSP-1 and G59-13 (PharMingen) for p53. Similar results were obtained with anti-TSP-1 antibody A4.1 (GIBCO BRL) (not shown).
Mentions: To first establish whether TSP-1 might be related to GD-AIF and mediate p53 control on angiogenesis, we examined whether p53 could regulate TSP-1 expression in glioblastoma cells. TSP-1 expression was analyzed in LN-Z308 glioblastoma cells, where p53 can be regulated by tetracycline 13. Cellular TSP-1 levels were measured in two clones conditionally inducible for p53 (wt4, wt11) in the presence (no induction) or absence (p53 induction) of tetracycline and in a control clone not inducible for p53 (wt1). The amounts of immunoprecipitated TSP-1 protein did not differ upon wt p53 induction in both wt4 and wt11 clones (Fig. 1). Moreover, Northern blotting on five glioblastoma cell lines with wt (U87MG, D247MG) or mutant (LN-229, LN-319, LN-Z308) TP53 alleles 30 did not show any correlation between TSP-1 mRNA expression and TP53 gene status (data not shown).

Bottom Line: Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells.This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors.This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Tumor Biology and Genetics, Neurosurgery Department, University Hospital (CHUV), 1011 Lausanne, Switzerland.

ABSTRACT
Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

Show MeSH
Related in: MedlinePlus