On the origin of serum CD26 and its altered concentration in cancer patients.
Dipeptidyl peptidase IV (DPP-IV), assigned to the CD26 cluster, is expressed on epithelial cells and lymphocytes and is a multifunctional or pleiotropic protein. Its peptidase activity causes degradation of many biologically active peptides, e.g. some incretins secreted by the enteroendocrine system. DPP-IV has, therefore, become a novel therapeutic target for inhibitors that extend endogenously produced insulin half-life in diabetics, and several reviews have appeared in recent months concerning the clinical significance of CD26/DPP-IV. Biological fluids contain relatively high levels of soluble CD26 (sCD26). The physiological role of sCD26 and its relation, if any, to CD26 functions, remain poorly understood because whether the process for CD26 secretion and/or shedding from cell membranes is regulated or not is not known. Liver epithelium and lymphocytes are often cited as the most likely source of sCD26. It is important to establish which tissue or organ is the protein source as well as the circumstances that can provoke an abnormal presence/absence or altered levels in many diseases including cancer, so that sCD26 can be validated as a clinical marker or a therapeutic target. For example, we have previously reported low levels of sCD26 in the blood of colorectal cancer patients, which indicated the potential usefulness of the protein as a biomarker for this cancer in early diagnosis, monitoring and prognosis. Through this review, we envisage a role for sCD26 and the alteration of normal peptidase capacity (in clipping enteroendocrine or other peptides) in the complex crosstalk between the lymphoid lineage and, at least, some malignant tumours.
Cordero
Oscar J
OJ
Department of Biochemistry and Molecular Biology, CIBUS, University of Santiago de Compostela, r/Lopez de Marzoa s/n, Campus Sur, 15782 Santiago de Compostela, Spain. oscarj.cordero@usc.es
Salgado
Francisco J
FJ
Nogueira
Montserrat
M
D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000502:physiology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D011480:Protease Inhibitors / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D011480:Protease Inhibitors; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4