Mapping of carboxypeptidase m in normal human kidney and renal cell carcinoma: expression in tumor-associated neovasculature and macrophages.

J Histochem Cytochem. 2013 Mar;61(3):218-35.

Denis CJ, Van Acker N, De Schepper S, De Bie M, Andries L, Fransen E, Hendriks D, Kockx MM, Lambeir AM.

Laboratory of Medical Biochemistry, University of Antwerp, Belgium.

 

Abstract

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney.

PMID: 23172796

 

Supplement:

The carboxypeptidase M (CPM) activity in urine most likely originates from CPM expressed by the tubular structures of the nephrons. The CPM gene is located in an unstable region of chromosome 12 that is amplified in certain kinds of solid tumors. Immunohistochemical (IHC) staining of CPM in normal kidney tissue sections shows that most cells are CPM positive but the IHC intensity is moderate. However, CPM staining of the tissue cores of the TMA LS-SKICA31 (Lifespan Biosciences) microarray reveals that in the majority of renal cell carcinoma CPM expression goes down when the cancer cells dedifferentiate. The figure shows bar charts of the mean IHC CPM intensity (A) and mean % CPM-stained cells (tumor or epithelial cells, B) (blue bars) with respect to the diagnosis. Non-tumoral renal disease groups and normal kidney groups were grouped at the end of the charts and are indicated with a red frame.

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