Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma.
BACKGROUND
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.


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.
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
F Q
FQ
Yang
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
M
M
Liu
Departamento de Medicina, People's Hospital in Xinyuan County Xinjiang Province, Xinjiang, China.
F P
FP
Yang
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
X L
XL
Zhang
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
B
B
Yang
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
C C
CC
Guo
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
J H
JH
Huang
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
J P
JP
Che
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Y
Y
Yan
Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: fengqiangyang@gmail.com.
J H
JH
Zheng
D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009363:Neoplasm Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D019139:Tumor Escape / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Carcinoma de células renales; MICA; MMP2; NKG2D; Renal cell carcinoma