Dataset Information

Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.

ABSTRACT:

Background

Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal cell tumors in a retrospective study.

Methods

Tumor and adjacent normal tissues of 395 nephrectomized patients were immunostained for RECK and EMMPRIN on a tissue microarray.

Results

RECK strongly decreased in renal cell carcinoma compared to normal counterparts (Wilcoxon signed rank test, P<0.001), and it discriminated tumor entities showing the highest expression in oncocytomas. EMMPRIN, however, could be significantly correlated to pT stage and Fuhrman grading (Spearman's correlation coefficient rs=0.289 and rs=0.382, respectively). Higher expression of EMMPRIN was associated with decreased overall survival in Kaplan-Meier analysis (P<0.001), and the EMMPRIN level could independently predict survival for cases without metastasis and involvement of lymph nodes. Decreased RECK expression was confirmed by Western blotting in tissue of eight normal/tumor matches of patients after radical nephrectomy, whereas the EMMPRIN pattern appeared to be heterogeneous.

Conclusions

We propose RECK down regulation in renal cell carcinoma to be an early event that facilitates tumor formation and progression. EMMPRIN, however, as a prognostic tumor marker, increases only when aggressiveness is proceeding and could add an additional step to invasive properties of renal cell carcinoma.

SUBMITTER: Rabien A

PROVIDER: S-EPMC3853196 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.

Rabien Anja A Stephan Carsten C Kilic Ergin E Weichert Wilko W Kristiansen Glen G Miller Kurt K Jung Klaus K Erbersdobler Andreas A

Journal of translational medicine 20131016

<h4>Background</h4>Matrix metalloproteinases can promote invasion and metastasis, which are very frequent in renal cell carcinoma even at the time of diagnosis. Knowing the reversion-inducing cysteine-rich protein with Kazal motifs (RECK) as an inhibitor of matrix metalloproteinases and the extracellular matrix metalloproteinase inducer (EMMPRIN) protein as inducer, we aimed to determine their expression, localization and possible antagonistic action in the pathogenesis and progression of renal ...[more]

PMID: 24131772

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Project description:BackgroundThe BRAF inhibitor vemurafenib (PLX) has shown promise in treating metastatic melanoma, but most patients develop resistance to treatment after 6 mo. We identified a transmembrane protein, extracellular matrix metalloproteinase inducer (EMMPRIN) as a cell surface receptor highly expressed by PLX-resistant melanoma. Using an S100A9 ligand, we created an EMMPRIN targeted probe and liposome that binds to melanoma cells in vivo, thus designing a novel drug delivery vehicle.MethodsPLX-resistant cells were established through continuous treatment with PLX-4032 over the course of 1 y. Both PLX-resistant and sensitive melanoma cell lines were evaluated for the expression of unique cell surface proteins, which identified EMMPRIN as an overexpressed protein in PLX0-resistant cells and S100A9 is a ligand for EMMPRIN. To design a probe for EMMPRIN, S100A9 ligand was conjugated to a CF-750 near-infrared (NIR) dye. EMMPRIN targeted liposomes were created to encapsulate CF-750 NIR dye. Liposomes were characterized by scanning electron microscopy, flow cytometry, and in vivo analysis. A2058PLX and A2058 cells were subcutaneously injected into athymic mice. S100A9 liposomes were intravenously injected and tumor accumulation was evaluated using NIR fluorescent imaging.ResultsWestern blot and flow cytometry demonstrated that PLX sensitive and resistant A2058 and A375 melanoma cells highly express EMMPRIN. S100A9 liposomes were 200 nm diameter and uniformly sized. Flow cytometry demonstrated 100X more intracellular dye uptake by A2058 cells treated with S100A9 liposomes compared with untargeted liposomes. In vivo accumulation of S100A9 liposomes within subcutaneous A2058 and A2058PLX tumors was observed from 6-48 h, with A2058PLX accumulating significantly higher levels (P = 0.001626).ConclusionsEMMPRIN-targeted liposomes via an S100A9 ligand are a novel, targeted delivery system which could provide improved EMMPRIN specific drug delivery to a tumor.

Dataset Information

Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.

Background

Methods

Results

Conclusions

Publications

Renal cell neoplasias: reversion-inducing cysteine-rich protein with Kazal motifs discriminates tumor subtypes, while extracellular matrix metalloproteinase inducer indicates prognosis.

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