?美国密歇根大学的研究小组最近发现了癌症细胞利用分子剪刀来向身体其它各处扩散的机制。这一由Kevin Hotary，Xiao-Yan Li，Edward Allen，Susan L.Stevens和Stephen J.Weiss完成的结果将发表在10月1日的刊物《Gene & Development》上。
??癌症细胞的扩散在医学上叫做转移，它是癌症发展过程中的一个重要转折点，在这之后治疗和恢复都变得非常困难。
??密歇根大学生命科学研究所教授Stephen Weiss表示：“我们一直在寻找癌症细胞是怎样在组织中找到出路的。它们利用了一种叫做分子剪刀的蛋白酶。但是从人类的基因组中可以制造出很多种不同的分子剪刀，我们主要目标是找出其中那些被癌症细胞用来扩散的基因。”
??所有的癌症细胞的共同恶性特征是：它们可以穿透基底膜层，这是一层在身体器官内外表面之间的特殊结缔组织，在血管、神经、肌肉和脂肪中都存在。而我们的身体中有超过500种的酶可以被细胞用来做分子剪刀，Weiss的小组发现了其中三种蛋白酶可能被癌症细胞用来入侵正常组织，它们是：MT1-MMP，MT2-MMP和MT3-MMP。
??癌症细胞用以上三种酶在结缔组织中切开通道，然后它们可以进入血管，进而扩散到全身的各处器官。Weiss说：“这些蛋白酶使得癌症细胞可以消耗掉基底膜和周围的部分组织。这是恶性肿瘤扩散关键的第一步，接下来就是癌细胞快速的转移到全身各处。”
??通过找到这些特定蛋白酶，Weiss和他的同事第一次证明了某些基因和蛋白质可以影响癌症细胞的转移过程。现在他们的工作还处于起步阶段，下面小组将主要致力于寻找这些蛋白酶的抑制剂，然后就可以在动物上进行人类肿瘤实验。
部分英文原文：
Matrix Metalloproteinases (MMPs) Regulate Fibrin-invasive Activity via MT1-MMP–dependent and –independent Processes
Cross-linked fibrin is deposited in tissues surrounding wounds, inflammatory sites, or tumors and serves not only as a supporting substratum for trafficking cells, but also as a structural barrier to invasion. While the plasminogen activator-plasminogen axis provides cells with a powerful fibrinolytic system, plasminogen-deleted animals use alternate proteolytic processes that allow fibrin invasion to proceed normally. Using fibroblasts recovered from wild-type or gene-deleted mice, invasion of three-dimensional fibrin gels proceeded in a matrix metalloproteinase (MMP)-dependent fashion. Consistent with earlier studies supporting a singular role for the membrane-anchored MMP, MT1-MMP, in fibrin-invasive events, fibroblasts from MT1-MMP–null mice displayed an early defect in invasion. However, MT1-MMP–deleted fibroblasts circumvented this early deficiency and exhibited compensatory fibrin-invasive activity. The MT1-MMP–independent process was sensitive to MMP inhibitors that target membrane-anchored MMPs, and further studies identified MT2-MMP and MT3-MMP, but not MT4-MMP, as alternate pro-invasive factors. Given the widespread distribution of MT1-, 2-, and 3-MMP in normal and neoplastic cells, these data identify a subset of membrane-anchored MMPs that operate in an autonomous fashion to drive fibrin-invasive activity.
更多原文链接：http://www.jem.org/cgi/content/full/195/3/295
