title: Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells.
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.
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Beckenkamp
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Júlia Biz
authors.initials: JB
authors.lastname: Willig
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Danielle Bertodo
authors.initials: DB
authors.lastname: Santana
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Jéssica
authors.initials: J
authors.lastname: Nascimento
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cancer Genomics Group, Cape Town, South Africa.
authors.forename: Juliano Domiraci
authors.initials: JD
authors.lastname: Paccez
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cancer Genomics Group, Cape Town, South Africa.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Zerbini
authors.affiliation: Federal Institute of Education, Science and Technology, Porto Alegre, RS, Brazil.
authors.forename: Alessandra Nejar
authors.initials: AN
authors.lastname: Bruno
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Diogo André
authors.initials: DA
authors.lastname: Pilger
authors.affiliation: Laboratory of Cell Biology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Márcia Rosângela
authors.initials: MR
authors.lastname: Wink
authors.affiliation: Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Andréia
authors.initials: A
authors.lastname: Buffon
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D000068900:Sitagliptin Phosphate / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D008562:Membrane Glycoproteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate