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Cell Death Differ. 2006 Sep;13(9):1442-53. Epub 2005 Nov 18.

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth.

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1
School of Biomedical and Natural Sciences, Nottingham Trent University, Nottingham NG11 8NS, UK.

Abstract

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

PMID:
16294209
DOI:
10.1038/sj.cdd.4401816
[Indexed for MEDLINE]
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