1. Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma.
- Author
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Yang FQ, Liu M, Yang FP, Zhang XL, Yang B, Guo CC, Huang JH, Che JP, Yan Y, and Zheng JH
- Subjects
- Blotting, Western, Carcinoma, Renal Cell chemistry, Carcinoma, Renal Cell immunology, Carcinoma, Renal Cell metabolism, Cell Line, Tumor, Gene Knockdown Techniques, Histocompatibility Antigens Class I analysis, Histocompatibility Antigens Class I immunology, Humans, Kidney Neoplasms chemistry, Kidney Neoplasms immunology, Kidney Neoplasms metabolism, Matrix Metalloproteinase 2 deficiency, NK Cell Lectin-Like Receptor Subfamily K metabolism, Neoplasm Proteins deficiency, Neoplasm Proteins immunology, RNA, Small Interfering pharmacology, Real-Time Polymerase Chain Reaction, Recombinant Fusion Proteins metabolism, Transfection, Carcinoma, Renal Cell pathology, Histocompatibility Antigens Class I metabolism, Kidney Neoplasms pathology, Matrix Metalloproteinase 2 physiology, Neoplasm Proteins physiology, Tumor Escape physiology
- 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., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)
- Published
- 2014
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