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Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer
B Göhring1, H J Holzhausen, A Meye
1Department of Urology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Abstract:
The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.
Insights
Renal cell cancer (RCC) shows altered expression of key membrane peptidases. Neutral endopeptidase 24.11 (NEP) is downregulated in clear cell RCC, impacting cancer progression.
Area of Science:
- Nephrology
- Oncology
- Biochemistry
Background:
- Malignant transformation in renal cell cancer (RCC) involves unclear regulatory mechanisms.
- Biologically active peptides may influence RCC behavior, modulated by tumor cell surface enzymes.
Purpose of the Study:
- To investigate the expression of membrane peptidases in RCC.
- To understand the role of these enzymes in RCC pathogenesis and progression.
Main Methods:
- Immunohistochemistry and enzyme-histochemistry were used.
- Examined membrane peptidase expression in 44 RCC samples and adjacent renal parenchyma.
Main Results:
- Neutral endopeptidase 24.11 (NEP) protein expression and activity were significantly downregulated in clear cell/chromophilic RCC.
- Dipeptidyl peptidase IV (DPIV) showed strong expression, decreased only in chromophobe RCC.
- Aminopeptidase N (APN) and Aminopeptidase A (APA) expression was attenuated in some clear cell RCC.
- Chromophobe RCC and oncocytomas lacked expression of APN, APA, NEP, and gamma-glutamyltranspeptidase.
Conclusions:
- Specific membrane peptidases, particularly NEP, exhibit altered expression patterns in different RCC subtypes.
- These peptidase alterations may play a role in RCC development and progression.
- Findings suggest potential diagnostic or therapeutic targets based on peptidase profiles.