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

R.A. Jones, P. Kotsakis, T.S. Johnson, D.Y.S. Chau, S. Ali, G. Melino, Martin Griffin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1442-1453
Number of pages12
JournalCell Death and Differentiation
Volume13
Issue number9
DOIs
Publication statusPublished - Sep 2006

Keywords

  • transglutaminase 2
  • inhibition
  • angiogenesis
  • solid tumor
  • extracellular matrix

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