Differential expression and enzymatic activity of DPPIV/CD26 affects migration ability of cervical carcinoma Cells

Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform. In the present study, we investigated DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26 expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was almost undetectable. We observed higher migratory capacity of HeLa, when compared to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration, indicating that, at least in part, cell migration is regulated by DPPIV/CD26 activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa cells exhibited a significant reduction in adhesion. However this mechanism seems to be mediated independent of DPPIV/CD26. This study demonstrates, for the first time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the effect of sitagliptin phosphate on cell migration and adhesion

Cell surface expression of DPPIV/CD26 protein determined by flow cytometry analysis.

<p>Immortalized keratinocytes, HaCaT (a), cervical cancer cells, SiHa (b), HeLa (c) and C33A (d) and lymphocytes extracted from whole blood (e). Cells were stained with the anti-human DPPIV/CD26 antibody FITC-conjugated. The Y-axis shows relative cell number and the X-axis shows the fluorescence intensity. The solid black line depicts DPPIV/CD26 expression and filled histogram is the unlabeled control. Histograms are representative from three independent experiments.</p