Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma
Actas Urol Esp. 2014 Apr;38(3):172-8.
doi: 10.1016/j.acuro.2013.09.015.
Epub 2014 Jan 22.
[Article in
English,
Spanish]
Affiliations
- 1 Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
- 2 Departamento de Medicina, People's Hospital in Xinyuan County Xinjiang Province, Xinjiang, China.
- 3 Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: fengqiangyang@gmail.com.
Abstract
Introduction:
The MHC class i chain-related molecule A (MICA) is a ligand for the natural killer group 2, member D (NKG2D) immunoreceptor activation. The engagement of tumor cell surface MICA to NKG2D stimulates the NK and T cell antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune evasion, which might partially contribute to tumor progression.
Material and methods:
Inmunohistochemistry was performed on both normal and neoplastic renal tissue. Human renal carcinoma cell lines 786-0 and ACHIN were transfected and target sequences to silence human MMP2 by shRNA expression were established. The degree of MICA shedding was measured and quantitative real-time PCR and Western-blot analysis were performed.
Results:
The membrane type matrix metalloproteinase 2 (MMP2) mediated the MICA shedding, which was blocked by suppression of MMP2 expression. Concomitantly, MMP2 over-expression enhanced the MICA shedding, indicating that MMP2 was involved in the renal cell carcinoma-associated proteolytic release of soluble MICA (sMICA), which facilitated the tumor immune escape.
Conclusions:
These findings suggested that MMP2 might be a new potential target for tumor immune therapy. Elucidation of the mechanisms by which tumors shed MICA could be of a great importance for cancer treatment in order to reinforce the NK and T cell antitumor immunity.
Keywords:
Carcinoma de células renales; MICA; MMP2; NKG2D; Renal cell carcinoma.
Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Carcinoma, Renal Cell / chemistry
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Carcinoma, Renal Cell / immunology
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Carcinoma, Renal Cell / metabolism
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Carcinoma, Renal Cell / pathology*
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Cell Line, Tumor
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Gene Knockdown Techniques
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Histocompatibility Antigens Class I / analysis
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Kidney Neoplasms / chemistry
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Kidney Neoplasms / immunology
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Kidney Neoplasms / metabolism
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Kidney Neoplasms / pathology*
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Matrix Metalloproteinase 2 / deficiency
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Matrix Metalloproteinase 2 / physiology*
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NK Cell Lectin-Like Receptor Subfamily K / metabolism
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / immunology
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Neoplasm Proteins / physiology*
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RNA, Small Interfering / pharmacology
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Real-Time Polymerase Chain Reaction
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Recombinant Fusion Proteins / metabolism
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Transfection
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Tumor Escape / physiology*
Substances
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Histocompatibility Antigens Class I
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KLRK1 protein, human
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MHC class I-related chain A
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NK Cell Lectin-Like Receptor Subfamily K
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Neoplasm Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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MMP2 protein, human
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Matrix Metalloproteinase 2