NDLI: Ensnaring membrane type 1-matrix metalloproteinase (MT1-MMP) with tissue inhibitor of metalloproteinase (TIMP)-2 using the haemopexin domain of the protease as a carrier: a targeted approach in cancer inhibition.

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Ensnaring membrane type 1-matrix metalloproteinase (MT1-MMP) with tissue inhibitor of metalloproteinase (TIMP)-2 using the haemopexin domain of the protease as a carrier: a targeted approach in cancer inhibition.

Content Provider	Europe PMC
Author	Jiang, Bingjie Zhang, Yan Liu, Jian Tsigkou, Anastasia Rapti, Magdalini Lee, Meng Huee
Copyright Year	2017
Abstract	Metastatic cancer cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) to degrade the extracellular matrix in order to facilitate migration and proliferation. Tissue Inhibitor of Metalloproteinase (TIMP)-2 is the endogenous inhibitor of the MMP. Here, we describe a novel and highly effective fusion strategy to enhance the delivery of TIMP-2 to MT1-MMP. We can reveal that TIMP-2 fused to the haemopexin +/− transmembrane domains of MT1-MMP (two chimeras named T2PEX+TM and T2PEX) are able to interact with MT1-MMP on the cell surface as well as intracellularly. In the case of T2PEX+TM, there is even a clear sign of MT1-MMP:T2PEX+TM aggregation by the side of the nucleus to form aggresomes. In vitro, T2PEX+TM and T2PEX suppress the gelatinolytic and invasive abilities of cervical carcinoma (HeLa) and HT1080 fibrosarcoma cancer cells significantly better than wild type TIMP-2. In mouse xenograft, we further demonstrate that T2PEX diminishes cervical carcinoma growth by 85% relative to the control. Collectively, our findings indicate the effectiveness of the fusion strategy as a potential targeted approach in cancer inhibition.
Journal	Oncotarget
Volume Number	8
PubMed Central reference number	PMC5410255
Issue Number	14
PubMed reference number	28186971
e-ISSN	19492553
DOI	10.18632/oncotarget.15165
Language	English
Publisher	Impact Journals LLC
Publisher Date	2017-04-01
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. Copyright: © 2017 Jiang et al.
Subject Keyword	MT1-MMP TIMP cancer haemopexin protein engineering
Content Type	Text
Resource Type	Article
Subject	Oncology

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