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Open Access Research article

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

Adolfo Varona1, Lorena Blanco1, Itxaro Perez1, Javier Gil1, Jon Irazusta1, José I López2, M Luz Candenas3, Francisco M Pinto3 and Gorka Larrinaga1*

Author Affiliations

1 Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Barrio Sarriena s/n, 48940-Leioa, Spain

2 Department of Anatomic Pathology, University Hospital of Cruces, Plaza de Cruces s/n, 48903-Cruces/Barakaldo, Spain

3 Institute for Chemical Research, CSIC-Isla de la Cartuja, Avd Americo Vespucio 49, 41092-Sevilla, Spain

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BMC Cancer 2010, 10:193  doi:10.1186/1471-2407-10-193

Published: 11 May 2010

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.