Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-24077

Tritschler, I; Gramatzki, D; Capper, D; Mittelbronn, M; Meyermann, R; Saharinen, J; Wick, W; Keski-Oja, J; Weller, M (2009). Modulation of TGF-beta activity by latent TGF-beta-binding protein 1 in human malignant glioma cells. International Journal of Cancer, 125(3):530-540.

[img]
Preview
PDF
2MB

View at publisher
[img]
Preview
Accepted Version
PDF
9MB

Abstract

High biological activity of the transforming growth factor (TGF)-beta-Smad pathway characterizes the malignant phenotype of malignant gliomas and confers poor prognosis to glioma patients. Accordingly, TGF-beta has become a novel target for the experimental treatment of these tumors. TGF-beta is processed by furin-like proteases (FLP) and secreted from cells in a latent complex with its processed propeptide, the latency-associated peptide (LAP). Latent TGF-beta-binding protein 1 (LTBP-1) covalently binds to this small latent TGF-beta complex (SLC) and regulates its function, presumably via interaction with the extracellular matrix (ECM). We report here that the levels of LTBP-1 protein in vivo increase with the grade of malignancy in gliomas. LTBP-1 is associated with the ECM as well as secreted into the medium in cultured malignant glioma cells. The release of LTBP-1 into the medium is decreased by the inhibition of FLP activity. Gene-transfer mediated overexpression of LTBP-1 in glioma cell lines results in an increase inTGF-beta activity. Accordingly, Smad2 phosphorylation as an intracellular marker of TGF-beta activity is enhanced. Conversely, LTBP-1 gene silencing reduces TGF-beta activity and Smad2 phosphorylation without affecting TGF-beta protein levels. Collectively, we identify LTBP-1 as an important modulator of TGF-beta activation in glioma cells, which may contribute to the malignant phenotype of these tumors.

Citations

10 citations in Web of Science®
11 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

131 downloads since deposited on 18 Nov 2009
28 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2009
Deposited On:18 Nov 2009 14:38
Last Modified:27 Nov 2013 22:19
Publisher:Wiley-Blackwell
ISSN:0020-7136
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1002/ijc.24443
PubMed ID:19431147

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page