Jones R A, Kotsakis P, Johnson T S, Chau D Y S, Ali S, Melino G, Griffin M
School of Biomedical and Natural Sciences, Nottingham Trent University, Nottingham NG11 8NS, UK.
Cell Death Differ. 2006 Sep;13(9):1442-53. doi: 10.1038/sj.cdd.4401816. Epub 2005 Nov 18.
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.
将活性转谷氨酰胺酶2（TG2）应用于两种不同的体外血管生成试验，导致复杂细胞外基质（ECM）的积累，从而抑制内皮细胞管形成，且不引起细胞死亡。基质积累伴随着ECM周转速率降低，对基质金属蛋白酶-1的抗性增加。向携带CT26结肠癌肿瘤的小鼠瘤内注射TG2，显示肿瘤生长减缓，在某些情况下肿瘤消退。在TG2基因敲除小鼠中，与野生型小鼠相比，肿瘤进展加快且存活率降低。在野生型小鼠中，肿瘤周围宿主组织中可检测到TG2的存在增加。对注射TG2的CT26肿瘤进行分析，发现含有增加的胶原蛋白、TG2介导的交联和减少的有组织脉管系统的纤维化样组织。TG2通过ECM变化介导的细胞行为调节可能为实体瘤治疗提供一种新方法。
