Mangala Lingegowda S, Arun Banu, Sahin Aysegul A, Mehta Kapil
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Mol Cancer. 2005 Sep 9;4:33. doi: 10.1186/1476-4598-4-33.
Alterations in the extracellular matrix (ECM) can affect host-tumor interactions and tumor growth and metastasis. Tissue transglutaminase (TG2, EC 2.3.2.13), a calcium-dependent enzyme that catalyzes covalent cross-linking of proteins, can render the ECM highly stable and resistant to proteolytic degradation. So we determined whether TG2 expression in a tumor or nontumor (stroma) environment could affect the process of metastasis. Two hundred archived samples from patients with breast cancer were studied for the TG2 expression. Also, in an in vitro model the invasive behavior of MDA-MB-231 cells in the presence or absence of exogenous TG2 was determined.
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.
细胞外基质（ECM）的改变会影响宿主与肿瘤的相互作用以及肿瘤的生长和转移。组织转谷氨酰胺酶（TG2，EC 2.3.2.13）是一种钙依赖性酶，可催化蛋白质的共价交联，能使细胞外基质高度稳定并抵抗蛋白水解降解。因此，我们确定肿瘤或非肿瘤（基质）环境中的TG2表达是否会影响转移过程。对200例乳腺癌患者的存档样本进行了TG2表达研究。此外，在体外模型中，测定了有无外源性TG2时MDA-MB-231细胞的侵袭行为。
与阴性淋巴结相关的肿瘤在基质中TG2表达显著更高（P < 0.001）。基质中的TG2具有催化活性，异肽交联的存在表明了这一点。用具有催化活性的TG2预处理基质胶可强烈抑制MDA-MB-231细胞通过基质胶Transwell小室滤膜的侵袭。
TG2诱导的细胞外基质改变可有效抑制转移过程。因此，在肿瘤部位选择性诱导具有催化活性的TG2可能为限制转移提供有前景的方法。
