Cell cycle-dependent nuclear location of the matricellular protein SPARC: Association with the nuclear matrix

Gooden, Michel D.; Vernon, Robert B.; Bassuk, James A.; Sage, E. Helene

doi:10.1002/(sici)1097-4644(19990801)74:2<152::aid-jcb2>3.0.co;2-4

Cited by 69 publications

(48 citation statements)

References 66 publications

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“…A recent report provides the evidence that the endocytosis of extracellular SPARC is followed by nuclear translocation. Therefore, it is also likely that SPARC exerts its effect intracellularly (24).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas

Seno

Harada²,

Kohno³

et al. 2009

Int J Oncol

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Abstract. The secreted protein acidic and rich in cysteine (SPARC) is a secreted glycoprotein that plays an essential role in promoting the motility of invasive tumor cells. In the present study, we investigated the role of SPARC in the motile and invasive activities of human glioma cells by silencing the SPARC gene. Introduction of SPARC-targeted small interfering RNA (siRNA) into glioma cell lines resulted in downregulation of SPARC expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with SPARC siRNA compared with those transfected with control siRNA. In an organotypic brain slice model, coculture of glioma spheroids and rat brain slices showed that SPARC siRNA-transfected glioma cells failed to invade the surrounding normal brain tissue. In addition, intracerebral injection of glioma cells transfected with SPARC siRNA in nude mice resulted in the formation of a non-invasive tumor, whereas injection of cells transfected with control siRNA resulted in diffuse invasive tumors. Since SPARC was exclusively expressed in the invasive zone of the tumor margin and the area surrounding tumor necrosis, we investigated the relationship between SPARC expression and hypoxic stress. SPARC expression was upregulated under hypoxic stress of 1% oxygen concentration in glioma cells. Silencing hypoxia-inducible factor-1· with siRNA reduced the overexpression of SPARC induced under hypoxic conditions. These results suggest that SPARC plays an essential role in the invasive activity of human glioma cells, under hypoxic conditions. Downregulation of SPARC may be a novel antiinvasion therapeutic strategy for malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas

Seno

Harada²,

Kohno³

et al. 2009

Int J Oncol

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“…(iv) SPARC could change the configuration of the extracellular matrix and/or the shape of the cell and could thus affect binding between a ligand and its cell-surface receptor. (v) Since SPARC has been shown to be associated with the nuclear matrix (48), it could be involved in the activation or suppression of gene expression and/or in the modulation of nuclear shape. These hypotheses are currently under investigation in our laboratory.…”

Section: Anti-tgf-␤1 Blocking Antibodies Reverse the Stimulatory Effementioning

confidence: 99%

SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-β1 in Mesangial Cells

Francki¹,

Bradshaw²,

Bassuk³

et al. 1999

Journal of Biological Chemistry

173

140

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The matricellular protein SPARC is expressed at high levels in cells that participate in tissue remodeling and is thought to regulate mesangial cell proliferation and extracellular matrix production in the kidney glomerulus in a rat model of glomerulonephritis (Pichler, R. H., Bassuk, J. A., Hugo, C., Reed, M. J., Eng, E., Gordon, K. L., Pippin, J., Alpers, C. E., Couser, W. G., Sage, E. H., and Johnson, R. J. (1997) Am. J. Pathol. 148, 1153-1167). A potential mechanism by which SPARC controls both cell cycle and matrix production has been attributed to its regulation of a pleiotropic growth factor. In this study we used primary mesangial cell cultures from wild-type mice and from mice with a targeted disruption of the SPARC gene. SPARC-null cells displayed diminished expression of collagen type I mRNA and protein, relative to wild-type cells, by the criteria of immunocytochemistry, immunoblotting, and the reverse transcription-polymerase chain reaction. The SPARC-null cells also showed significantly decreased steady-state levels of transforming growth factor-␤1 (TGF-␤1) mRNA and secreted TGF-␤1 protein. Addition of recombinant SPARC to SPARC-null cells restored the expression of collagen type I mRNA to 70% and TGF-␤1 mRNA to 100% of wildtype levels. We conclude that SPARC regulates the expression of collagen type I and TGF-␤1 in kidney mesangial cells. Since increased mitosis and matrix deposition by mesangial cells are characteristics of glomerulopathies, we propose that SPARC is one of the factors that maintains the balance between cell proliferation and matrix production in the glomerulus.

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“…The role of nuclear matrix in cell activities has drawn increasing attention recently. Most of its components, besides the fibrins, are proteins and/or enzyme in DNA replication, transcription and gene expression [3,4] . The nuclear matrix in cancer cells is not only abnormal in morphology, but also apparently different in its composition.…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells

Zhao

Li²

2005

WJG

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Abstract Abstract AbstractAIM: To find and identify specific nuclear matrix proteins associated with proliferation and differentiation of carcinoma cells, which will be potential markers for cancer diagnosis and targets in cancer therapy. METHODS:Nuclear matrix proteins were selectively extracted from MGc80-3 cells treated with or without hexamethylamine bisacetamide (HMBA), and subjected to 2-D gel electrophoresis. The resulted protein patterns were analyzed by Melanie software. Spots of nuclear matrix proteins differentially expressed were excised and subjected to in situ digestion with trypsin. Peptide masses were obtained by matrix-assisted laser-desorption/ ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis and submitted for database searching using Mascot tool. RESULTS:The MGc80-3 cells were induced into differentiation by HMBA. There were 22 protein spots which changed remarkably in the nuclear matrix, from differentiation of MGc80-3 cells compared to control. Eleven of which were identified. Seven proteinsactin, prohibitin, porin 31HL, heterogeneous nuclear ribonucleoprotein A2/B1, vimentin, ATP synthase, and heat shock protein 60 were downregulated, whereas three proteins -heat shock protein gp96, heat shock protein 90-beta, and valosin-containing protein were upregulated, and the oxygen-regulated protein was only found in the differentiated MGc80-3 cells. CONCLUSION:The induced differentiation of carcinoma cells is accompanied by the changes of nuclear matrix proteins. Further characterization of those proteins will show the mechanism of cellular proliferation and differentiation, as well as cancer differentiation.

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Cell cycle-dependent nuclear location of the matricellular protein SPARC: Association with the nuclear matrix

Cited by 69 publications

References 66 publications

Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas

Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas

SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-β1 in Mesangial Cells

Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells

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