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Inicio Actas Urológicas Españolas (English Edition) Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequen...
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Vol. 38. Issue 3.
Pages 172-178 (April 2014)
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Vol. 38. Issue 3.
Pages 172-178 (April 2014)
Original article
Matrix metallopeptidase 2 (MMP2) mediates MHC class I polypeptide-related sequence A (MICA) shedding in renal cell carcinoma
Matrix metallopeptidase 2 (MMP2) media la eliminación de MHC class I polypeptide-related sequence A (MICA) en el cáncer de células renales
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F.Q. Yanga,c, M. Liua, F.P. Yangb,c, X.L. Zhanga, B. Yanga, C.C. Guoa, J.H. Huanga, J.P. Chea, Y. Yana, J.H. Zhenga,
Corresponding author
fengqiangyang@gmail.com

Corresponding author.
a Departamento de Urología, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
b Departamento de Medicina, People's Hospital in Xinyuan County Xinjiang Province, Xinjiang, China
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Table 1. Immunohistochemical expression of MICA in renal cell carcinoma and normal renal tissues.
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 tissues. 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 overexpression 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:
Renal cell carcinoma
MICA
MMP2
NKG2D
Abbreviations:
RCC
PCR
786-O
ACHN
MMP2
MICA
NKG2D
Resumen
Introducción

La molécula A relacionada con la cadena de clase i del CMH (MICA) es un ligando del grupo 2 de células asesinas naturales, y miembro D (NKG2D) de la activación de inmunorreceptores. La unión de la superficie de la célula tumoral MICA con NKG2D estimula las células asesinas (NK) y la inmunidad de las células T antitumorales. La eliminación de MICA por las células tumorales facilita la evasión inmune del tumor, lo cual podría contribuir en parte a la progresión tumoral.

Materiales y métodos

Se aplicó inmunohistoquímica tanto en tejidos renales normales como neoplásicos. Se transfectaron las líneas de células tumorales de riñón humano 786-O y ACHIN, y se establecieron secuencias objetivo para silenciar la MMP2 humana a través de la expresión ARNhc. Se midió el grado de eliminación de MICA y se llevó a cabo una PCR cuantitativa en tiempo real, así como el análisis de Western blot.

Resultados

La membrana de tipo metaloproteinasa de matriz-2 (MMP2) media en la eliminación de MICA, que se bloquea por la supresión de la expresión de MMP2. Simultáneamente, la sobreexpresión de MMP2 aumenta la eliminación de MICA, lo cual indica que MMP2 interviene en la liberación proteolítica de MICA soluble (sMICA) asociada al carcinoma de células renales, que facilita el escape tumoral inmune.

Conclusiones

Dichos resultados sugieren que MMP2 podría ser un nuevo objetivo potencial para la terapia inmune de tumores. Un esclarecimiento de los mecanismos por los que los tumores eliminan MICA podría ser de gran importancia para el tratamiento del cáncer, para así reforzar las NK y la inmunidad antitumoral de las células T.

Palabras clave:
Carcinoma de células renales
MICA
MMP2
NKG2D

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