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Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma

¹Department of Physiology, Faculty of Medicine and Dentistry, ²Department of Nursing I, Nursing School, and ³Department of Pathology, Hospital de Basurto, University of the Basque Country, Bilbao, Spain

Submitted 27 April 2006 ; accepted in final form 15 September 2006

Peptides play important roles in cell regulation and signaling in many tissues and are regulated by peptidases, most of which are highly expressed in the kidney. Several peptide convertases have a function in different tumor stages, and some have been clearly characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however, little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in human tumor samples and nontumor tissue obtained from clear cell renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and subcellular distribution of peptide-converting activity, acid, neutral, basic, and omega activities were selected. CCRCC displays a selective and restricted pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t = 6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein; P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer. The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an intracrine renin-angiotensin system in the pathogenesis of CCRCC.

angiotensin II; peptide hormones; intracrine peptide signaling; peptide metabolism; renal tumor cell biology

This article has been cited by other articles:

				L. Blanco, G. Larrinaga, I. Perez, J. I. Lopez, J. Gil, E. Agirregoitia, and A. Varona Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma Am J Physiol Renal Physiol, April 1, 2008; 294(4): F850 - F858. [Abstract] [Full Text] [PDF]