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基质金属蛋白酶与肺癌的关系
引用本文:钟小军,杨瑞森,魏树臻. 基质金属蛋白酶与肺癌的关系[J]. 中华肿瘤防治杂志, 2006, 13(18): 1432-1435
作者姓名:钟小军  杨瑞森  魏树臻
作者单位:山东省肿瘤医院胸外科,山东,济南,250117;山东省肿瘤医院胸外科,山东,济南,250117;山东省肿瘤医院胸外科,山东,济南,250117
摘    要:基质金属蛋白酶(MMPs)是一类高度保守的锌离子依赖内肽酶家族,大部分能降解基底膜成分和细胞外基质,它在肿瘤的侵袭转移中起到了重要的作用。根据结构和底物的不同可以将现已发现的人类MMPs分为胶原酶类、明胶酶类、基质溶解素和膜型MMPs。MMPs有3个结构区域:N端的前肽区、催化区和C端的类血结区。MT-MMPs还有C端的跨膜区。MMPs激活的过程伴随着氨基端前肽区的裂解,而MMPs组织抑制因子(TIMPs)则是金属蛋白酶的主要抑制物。TIMPs有4种,分别被命名为TIMP1~TIMP4,与MMPs结合形成1∶1复合物,抑制其活性。MMPs/TIMPs的表达与肺癌的生长、侵袭和转移等特性有关,通过不同方法检测MMPs的活性有助于肺癌的预后判断,抑制MMPs的活性则能够抑制肿瘤的生长及侵袭能力。MMPs抑制剂的出现为肿瘤治疗提供了新的方法。

关 键 词:金属蛋白酶类  肺肿瘤  综述文献
文章编号:1673-5269(2006)18-1432-04
收稿时间:2006-01-08
修稿时间:2006-03-12

Relationship between matrix metalloproteinases and lung cancer
ZHONG Xiao-jun,YANG Rui-sen,WEI Shu-zhen. Relationship between matrix metalloproteinases and lung cancer[J]. Chinese Journal of Cancer Prevention and Treatment, 2006, 13(18): 1432-1435
Authors:ZHONG Xiao-jun  YANG Rui-sen  WEI Shu-zhen
Abstract:The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMPs are essential enzymes which are involved in the degradation of basilar membrane and the extracellular matrix, and play an important role in the tumor invasion and metastasis. Currently, at least 26 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Most members of the MMP family are organized into three domains based on structural considerations: an amino-terminal propeptide; a catalytic domain; and a hemopexin-like domain at the carboxy-terminal. The process of activation involves sequential cleavage of the propeptide, and proteolytic activity is inhibited by tissue inhibitors known as tissue inhibitors of metalloproteinase (TIMPs). the TIMP family, which presently includes four proteins: TIMP-1, TIMP-2, TIMP-3, and TIMP-4, inhibits protease activity by forming high-affinity 1:1 complexes with the MMPs. Recent data from model systems suggest that MMPs/TIMPs are involved in lung cancer initiation, invasion and metastasis. Consistent with their role in lung cancer progression, high levels of several MMPs have been found to correlate with poor prognosis in patients with lung cancer. Because MMPs are apparently involved in lung cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing lung cancer and in blocking metastasis of established tumours.
Keywords:metalloproteinases  lung neoplasms  review literature
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