Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent.
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.
Varona
Adolfo
A
Department of Physiology, Faculty of Medicine and Dentistry, University of Basque Country, Barrio Sarriena s/n, 48940-Leioa, Spain.
Blanco
Lorena
L
Perez
Itxaro
I
Gil
Javier
J
Irazusta
Jon
J
López
José I
JI
Candenas
M Luz
ML
Pinto
Francisco M
FM
Larrinaga
Gorka
G
D018249:Adenoma, Oxyphilic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015260:Neprilysin / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D015260:Neprilysin
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