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Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma.
- Source :
-
Actas urologicas espanolas [Actas Urol Esp] 2014 Apr; Vol. 38 (3), pp. 172-8. Date of Electronic Publication: 2014 Jan 22. - Publication Year :
- 2014
-
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.<br />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.<br />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.<br />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.<br /> (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)
- 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
Subjects
Details
- Language :
- English; Spanish; Castilian
- ISSN :
- 1699-7980
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Actas urologicas espanolas
- Publication Type :
- Academic Journal
- Accession number :
- 24461475
- Full Text :
- https://doi.org/10.1016/j.acuro.2013.09.015