Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC

Vajkoczy, Peter; Menger, Michael D.; Goldbrunner, Roland; Ge, Shugang; Fong, T. Annie T.; Vollmar, Brigitte; Schilling, Lothar; Ullrich, Axel; Hirth, K. Peter; Tonn, Jörg C.; Schmiedek, Peter; Rempel, Sandra A.

doi:10.1002/1097-0215(20000715)87:2<261::aid-ijc18>3.0.co;2-6

Cited by 67 publications

(44 citation statements)

References 21 publications

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“…This protein has a major role in the promotion of glioma cell invasion, as confirmed by evidence that human glioma cells engineered to over-express SPARC adopt an invasive phenotype [16]. A further interesting role for SPARC in the promotion of tumor progression has also recently been suggested [45]: it may enable tumor cells to survive under the stressful conditions that surround the tumor, such as nutrient restriction, hypoxia and genomic instability.…”

Section: Discussionmentioning

confidence: 88%

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Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells

Gagliano

Moscheni

Torri

et al. 2005

Biomedicine & Pharmacotherapy

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Section: Discussionmentioning

confidence: 88%

“…SPARC also takes part in proteolytic pathways by increasing the expression of collagenase and MMP-9, and activating MMP-2 [13]. This protein is frequently over-expressed in gliomas and its expression correlates with glioma invasion in vitro and in vivo [14][15][16]. SPARC may be a marker of invading cells.…”

Section: Introductionmentioning

confidence: 99%

Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells

Gagliano

Moscheni

Torri

et al. 2005

Biomedicine & Pharmacotherapy

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“…1-3) (Lane et al, 1994;, as it does in other developing tissues, and in tumors and dermal wounds (Lane et al, 1994;Iruela-Arispe et al, 1995;Vajkoczy et al, 2000;Chlenski et al, 2002). SPARC negatively regulates signaling by several angiogenic growth factors, including platelet derived growth factor (Motamed et al, 2002) and vascular endothelial growth factor (Kupprion et al, 1998), but can also be cleaved to produce the potent pro-angiogenic peptide (K)GHK (Lane et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

Vincent

Lau

Roskams

2008

Developmental Dynamics

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SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that is highly expressed during development, tissue remodeling, and repair. SPARC produced by olfactory ensheathing cells (OECs) can promote axon sprouting in vitro and in vivo. Here, we show that in the developing nervous system of the mouse, SPARC is expressed by radial glia, blood vessels, and other pial-derived structures during embryogenesis and postnatal development. The rostral migratory stream contains SPARC that becomes progressively restricted to the SVZ in adulthood. In the adult CNS, SPARC is enriched in specialized radial glial derivatives (Mü ller and Bergmann glia), microglia, and brainstem astrocytes. The peripheral glia, Schwann cells, and OECs express SPARC throughout development and in maturity, although it appears to be down-regulated with maturation. These data suggest that SPARC may be expressed by glia in a spatiotemporal manner consistent with a role in cell migration, neurogenesis, synaptic plasticity, and angiogenesis.

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“…Interestingly, gene array data from cells treated with TRAIL showed decreased expression of the invasiveness inhibitor protein SPARC. Although the latter normally inhibits cell invasiveness processes (Hasselaar and Sage, 1992), it displays opposite effects in tumour cells (Briggs et al, 2002), including glioblastoma (Vajkoczy et al, 2000). For this reason, SPARC has been regarded as an enhancer of the capability of glioblastomas to localise in multiple sites of the brain (Schultz et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells

et al. 2006

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Tumour growth is tightly related to new blood vessel formation, tissue remodelling and invasiveness capacity. A number of tissular factors fuel the growth of glioblastoma multiforme, the most aggressive brain neoplasm. In fact, gene array analyses demonstrated that the proapoptotic cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibited mRNA expression of VEGF, along with those of matrix metalloproteinase-2 (MMP-2), its inhibitor tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), as well as the tumour invasiveness-related gene secreted protein acid rich in cysteine (SPARC) in different human glioblastoma cell lines. Particularly, VEGF mRNA and protein expression and release from glioblastoma cells were also inhibited by TRAIL. The latter also exerted antimitogenic effects on human umbilical vein endothelial cells (HUVECs). With the same cells, TRAIL inhibited new vessel formation in the in vitro matrigel model, as well as it exerted powerful inhibition of blood vessel formation induced by an angiogenic cocktail administered in subcutaneous pellets in vivo in the C57 mouse. Moreover, the expression of MMP-2, its inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were effectively inhibited by TRAIL in glioblastoma cell lines. In conclusion, our data indicate that TRAIL inhibits the orchestra of factors contributing to glioblastoma biological aggressiveness. Thus, the TRAIL system could be regarded as a molecular target to exploit for innovative therapy of this type of tumour.

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Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC

Cited by 67 publications

References 21 publications

Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells

Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells

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