title: Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma.
abstract: 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.
authors.affiliation: Dept. of Physiology, Faculty of Medicine and Dentistry, Hospital de Basurto, University of the Basque Country, E-48080 Bilbao, Bizkaia, Spain. adolfo.varona@ehu.es
authors.forename: Adolfo
authors.initials: A
authors.lastname: Varona
authors.forename: Lorena
authors.initials: L
authors.lastname: Blanco
authors.forename: José I
authors.initials: JI
authors.lastname: López
authors.forename: Javier
authors.initials: J
authors.lastname: Gil
authors.forename: Ekaitz
authors.initials: E
authors.lastname: Agirregoitia
authors.forename: Jon
authors.initials: J
authors.lastname: Irazusta
authors.forename: Gorka
authors.initials: G
authors.lastname: Larrinaga
mesh_terms: D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000096:biosynthesis; D018826:CD13 Antigens / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D043384:Glutamyl Aminopeptidase / Q000096:biosynthesis; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D011751:Pyroglutamyl-Peptidase I / Q000096:biosynthesis
chemical_list: D010447:Peptide Hydrolases; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme; D018826:CD13 Antigens; C019721:aminopeptidase B; D043384:Glutamyl Aminopeptidase; D011751:Pyroglutamyl-Peptidase I