Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells

PLoS One. 2015 Jul 29;10(7):e0134305. doi: 10.1371/journal.pone.0134305. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Female
  • HeLa Cells
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Membrane Glycoproteins / metabolism
  • Sitagliptin Phosphate / pharmacology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Membrane Glycoproteins
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Sitagliptin Phosphate

Grants and funding

This work was supported by grants from Pharmaceutical Sciences Graduate Program (PPGCF/UFRGS), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Auxílio Recém-Doutor 0902665), Pró-Reitoria de Pesquisa-UFRGS (PROPESQ-UFRGS) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Procad-CAPES, Edital n° 071/2013 - 15819). A. Beckenkamp was a recipient of fellowships from Conselho de Desenvolvimento Científico e Tecnológico (CNPq-Brasil) and CAPES-Brazil, and J. Paccez was a recipient of postdoctoral fellowship from ICGEB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.