The extracellular matrix protein fibronectin is a substrate for kallikrein 7
The extracellular matrix protein fibronectin is a substrate for kallikrein 7
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DOI：
10.1016/j.bbrc.2008.03.021
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发表时间：
2008-05-16
影响因子：
3.1
通讯作者：
Haun, Randy S.
中科院分区：
文献类型：
--
作者：
Ramani, Vishnu C.;Haun, Randy S.
激肽释放酶7（hK7），一种凝乳蛋白样丝氨酸蛋白酶，在胰腺癌以及其他人类癌症中过表达。虽然它已被证明通过促进皮肤表面的细胞脱落参与正常脱屑，但其在人类恶性肿瘤中的作用仍不清楚。为了研究hK7降解细胞外基质（ECM）组分的能力，从培养的哺乳动物细胞表达并纯化重组hK7。使用三步色谱纯化程序，获得重组hK7，其在由嗜热菌蛋白酶激活后对荧光肽底物显示出稳健的蛋白水解活性。我们证明，活性蛋白酶是能够裂解纤连蛋白在一个时间依赖性的方式，但不是层粘连蛋白，使用体外降解试验。这些发现表明，hK7在人类肿瘤中的异常表达和分泌可能通过直接降解细胞外基质的组分而促进转移，因此可能在肿瘤发生中起重要作用。(C)2008年爱思唯尔公司All rights reserved.
Kallikrein 7 (hK7), a chymostatin-like serine protease, is overexpressed in pancreatic adenocarcinomas as well as other human cancers. Although it has been demonstrated to participate in normal desquamation by facilitating cell shedding at the skin surface, its role in human malignancies remains unclear. To investigate the ability of hK7 to degrade components of the extracellular matrix (ECM), recombinant hK7 was expressed and purified from cultured mammalian cells. Using a three-step chromatographic purification procedure, recombinant hK7 was obtained that displayed robust proteolytic activity against a fluorogenic peptide substrate following activation by thermolysin. We demonstrate that the active protease is able to cleave fibronectin in a time-dependent manner, but not laminin, using an in vitro degradation assay. These findings indicate that the aberrant expression and secretion of hK7 in human tumors may facilitate metastasis by directly degrading components of the extracellular matrix and may thus play an important role in tumorigenesis. (C) 2008 Elsevier Inc. All rights reserved.