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Comparative Study
. 2010 May 11:10:193.
doi: 10.1186/1471-2407-10-193.

Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent

Adolfo Varona  1 , Lorena Blanco, Itxaro Perez, Javier Gil, Jon Irazusta, José I López, M Luz Candenas, Francisco M Pinto, Gorka Larrinaga
Affiliations
Comparative Study

Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent

Adolfo Varona et al. BMC Cancer. .

Abstract

Background: Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO).

Methods: Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining.

Results: The activity of both glycoproteins was sharply decreased in the three histological types of renal tumors. Protein and mRNA expression was strongly downregulated in tumors from distal nephron (ChRCC and RO). Moreover, soluble DPP IV activity positively correlated with the aggressiveness of CCRCCs (higher activities in high grade tumors).

Conclusions: These results support the pivotal role for DPP IV and NEP in the malignant transformation pathways and point to these peptidases as potential diagnostic markers.

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Figures

Figure 1
Figure 1
Soluble (A) and membrane-bound DPP IV (B), and NEP (C) peptidase activity profiles in clear cell renal cell carcinoma (CCRCC), chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Columns compare tumor with non-tumor surrounding tissue (normal). Values represent mean ± SE of units of peptidase (UP) per milligram of protein.
Figure 2
Figure 2
Soluble (s) and membrane-bound DPP IV (A), and NEP (B) peptidase activity profiles in different grades and stages of clear cell renal cell carcinoma (CCRCC). Columns compare high grade (G3-G4) and stage (T3-T4) tumors with low grade (G1-G2) and stage (T1-T2) tumors. Values represent mean ± SE of units of peptidase (UP) per milligram of protein.
Figure 3
Figure 3
mRNA levels of DPP IV (A) and NEP (B) measured in tumour and nontumour tissue (normal) for CCRCC (n = 16), ChRCC (n = 6) and RO (n = 4) patients. RT-PCR data for each analyzed sample are recorded as relative units. The mean ± SE, p values and "normal/tumour" ratio of expression levels are also represented. *Statistically significant. ns no significant.
Figure 4
Figure 4
mRNA levels of DPP IV (A) and NEP (B) measured in different grades and stages of clear cell renal cell carcinoma (CCRCC). RT-PCR data for each analyzed sample are recorded as relative units. The mean ± SE, p values and "normal/tumour" ratio of expression levels are also represented. *Statistically significant. ns no significant.
Figure 5
Figure 5
Immunohistochemistry of DPP IV and NEP in renal tumors. Hematoxylin and eosin staining of CCRCC (A), ChRCC (D) and RO (G). DPP IV/CD26 staining of CCRCC (B), ChRCC (E) and RO (H). NEP staining of CCRCC (C), ChRCC (F) and RO (I). Tissues magnification at 400×.
Figure 6
Figure 6
Immunohistochemistry of DPP IV and NEP in normal renal tissue. DPP IV immunostainings are selectively located in proximal tubules. Tissues magnification at 400×
Figure 7
Figure 7
Immunohistochemistry of DPP IV and NEP in normal renal tissue. NEP immunostainings are selectively located in proximal tubules. Tissues magnification at 400×
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