%0 Journal Article
%T Tissue transglutaminase-induced alterations in extracellular matrix inhibit tumor invasion
%A Lingegowda S Mangala
%A Banu Arun
%A Aysegul A Sahin
%A Kapil Mehta
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-33
%X Tumors associated with negative nodes showed significantly higher expression of TG2 in the stroma (P < 0.001). TG2 in the stroma was catalytically active, as revealed by the presence of isopeptide cross-links. Pretreatment of Matrigel with catalytically active TG2 resulted in strong inhibition of invasion of MDA-MB-231 cells through the Matrigel Transwell filters.TG2-induced alterations in the ECM could effectively inhibit the process of metastasis. Therefore, selective induction of catalytically active TG2 at the site of tumor may offer promising approach for limiting the metastasis.Despite significant advances in the treatment of primary breast cancer, predicting and preventing metastasis remains a daunting clinical challenge. To make progress in this area, it is imperative to understand the molecular mechanisms that regulate the progression from a primary tumor to metastatic disease.Metastasis is a multistep process that involves intravasation, adhesion to a blood vessel wall, extravasation, infiltration, and the proliferation of cancer cells in the target tissue [1]. Many of these steps require interaction between tumor cells and the extracellular matrix (ECM). For example, the ECM can modulate tumor cell growth by binding to and storing cytokines, it can promote cell attachment and migration by providing a stable foundation, and it can support cell growth and survival by interacting with cell-surface receptors and activating appropriate signaling pathways [2,3].Several lines of evidence have suggested that tissue transglutaminase (TG2, EC 2.3.2.13) plays an important role in stabilizing the ECM by cross-linking its component proteins and rendering it resistant to mechanical and proteolytic degradation [4-7]. TG2, a member of the Ca2+-dependent family of mammalian enzymes, catalyzes irreversible cross-linking of proteins by inserting highly stable ¦Å(¦Ã-glutamyl)lysine bonds between them [5,8,9]. Several ECM proteins, such as fibronectin, vitronectin, collagen, fi
%U http://www.molecular-cancer.com/content/4/1/33