?美國密歇根大學(xué)的研究小組最近發(fā)現(xiàn)了癌癥細(xì)胞利用分子剪刀來向身體其它各處擴(kuò)散的機(jī)制,。這一由Kevin Hotary,，Xiao-Yan Li，Edward Allen,，Susan L.Stevens和Stephen J.Weiss完成的結(jié)果將發(fā)表在10月1日的刊物《Gene & Development》上,。
??癌癥細(xì)胞的擴(kuò)散在醫(yī)學(xué)上叫做轉(zhuǎn)移，它是癌癥發(fā)展過程中的一個重要轉(zhuǎn)折點(diǎn),，在這之后治療和恢復(fù)都變得非常困難,。
??密歇根大學(xué)生命科學(xué)研究所教授Stephen Weiss表示：“我們一直在尋找癌癥細(xì)胞是怎樣在組織中找到出路的。它們利用了一種叫做分子剪刀的蛋白酶,。但是從人類的基因組中可以制造出很多種不同的分子剪刀,，我們主要目標(biāo)是找出其中那些被癌癥細(xì)胞用來擴(kuò)散的基因。”
??所有的癌癥細(xì)胞的共同惡性特征是：它們可以穿透基底膜層,，這是一層在身體器官內(nèi)外表面之間的特殊結(jié)締組織,，在血管,、神經(jīng),、肌肉和脂肪中都存在。而我們的身體中有超過500種的酶可以被細(xì)胞用來做分子剪刀,，Weiss的小組發(fā)現(xiàn)了其中三種蛋白酶可能被癌癥細(xì)胞用來入侵正常組織,，它們是：MT1-MMP，MT2-MMP和MT3-MMP,。
??癌癥細(xì)胞用以上三種酶在結(jié)締組織中切開通道,，然后它們可以進(jìn)入血管，進(jìn)而擴(kuò)散到全身的各處器官。Weiss說：“這些蛋白酶使得癌癥細(xì)胞可以消耗掉基底膜和周圍的部分組織,。這是惡性腫瘤擴(kuò)散關(guān)鍵的第一步,，接下來就是癌細(xì)胞快速的轉(zhuǎn)移到全身各處。”
??通過找到這些特定蛋白酶,，Weiss和他的同事第一次證明了某些基因和蛋白質(zhì)可以影響癌癥細(xì)胞的轉(zhuǎn)移過程?，F(xiàn)在他們的工作還處于起步階段，下面小組將主要致力于尋找這些蛋白酶的抑制劑,，然后就可以在動物上進(jìn)行人類腫瘤實驗,。
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.
更多原文鏈接：http://www.jem.org/cgi/content/full/195/3/295
