Dipeptidyl Peptidase IV as a Novel Prognostic Marker and Important Therapeutic Target in Melanoma

Abstract

BackgroundThere is a lot of evidence which suggests that DPP IV level may correlate with a type of tumor cells, metastatic potential and prognosis for the patient. Bearing in mind that the melanomas are characterized by high heterogeneity and identification of specific phenotypes of cells allows for early and more effective therapy, the aim of our study was to check whether there is a correlation between the DPPIV and the metastatic potential of melanoma cell lines. Additionally, the aim of our research was to evaluate the anti-tumor potential of linagliptin and saxagliptin in melanoma cell lines as well as determining correlation between cytotoxicity of the drugs and DPP IV level. MethodsThe inhibitory effect of tested drugs on the cancer cell growth was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) while cell cycle analysis and apoptosis were performed using the NucleoCounter® NC-3000™ system (ChemoMetec, Denmark), following the instructions provided by the manufacturer. DPPIV release by cancer cells was measured by DPP4/CD26 ELISA assay kit for biological samples (Cloud-Clone Corp.,Wuhan,China). ResultsOur results showed that DPPIV overexpression promoted cell proliferation of melanoma cells. Our data showed that especially short term treatment with linagliptin is associated with not only decreased expression of DPPIV and inhibition of cell proliferation but also induction of cell cycle disruption and apoptosis in melanoma. ConclusionsThe routine identification of this glycoprotein in melanoma would be fundamental to assessing not only the risk of metastasis/disease progression but also selection of therapy and evaluation of its effectiveness.