Open Access Highly Accessed Research article

Altered glutamyl-aminopeptidase activity and expression in renal neoplasms

Lorena Blanco1, Begoña Sanz1, Itxaro Perez12, Clara E Sánchez2, M Luz Cándenas3, Francisco M Pinto3, Javier Gil1, Luis Casis1, José I López4 and Gorka Larrinaga12*

Author Affiliations

1 Department of Physiology, Faculty of Medicine and Dentistry, Universitiy of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

2 Department of Nursing I, Faculty of Nursing, Universitiy of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain

3 Institute for Chemical Research, CSIC, Sevilla, Spain

4 Department of Anatomic Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain

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BMC Cancer 2014, 14:386  doi:10.1186/1471-2407-14-386

Published: 30 May 2014

Abstract

Background

Advances in the knowledge of renal neoplasms have demonstrated the implication of several proteases in their genesis, growth and dissemination. Glutamyl-aminopeptidase (GAP) (EC. 3.4.11.7) is a zinc metallopeptidase with angiotensinase activity highly expressed in kidney tissues and its expression and activity have been associated wtih tumour development.

Methods

In this prospective study, GAP spectrofluorometric activity and immunohistochemical expression were analysed in clear-cell (CCRCC), papillary (PRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytoma (RO). Data obtained in tumour tissue were compared with those from the surrounding uninvolved kidney tissue. In CCRCC, classic pathological parameters such as grade, stage and tumour size were stratified following GAP data and analyzed for 5-year survival.

Results

GAP activity in both the membrane-bound and soluble fractions was sharply decreased and its immunohistochemical expression showed mild staining in the four histological types of renal tumours. Soluble and membrane-bound GAP activities correlated with tumour grade and size in CCRCCs.

Conclusions

This study suggests a role for GAP in the neoplastic development of renal tumours and provides additional data for considering the activity and expression of this enzyme of interest in the diagnosis and prognosis of renal neoplasms.

Keywords:
Glutamyl-aminopeptidase; Aminopeptidase A; Angiotensinase; Angiotensin; Clear cell renal cell carcinoma; Renal neoplasm