Matrix metallopeptidase 2 (MMP2) media la eliminación de MHC class I polypeptide-related sequence A (MICA) en el cáncer de células renales

Abstract

IntroductionThe 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 methodsInmunohistochemistry 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. ResultsThe 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. ConclusionsThese 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.