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Published on: October 5, 2014
Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells
Aline Beckenkamp1, Júlia Biz Willig1, Danielle Bertodo Santana1
1Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
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.
Insights
Dipeptidyl peptidase IV (DPPIV/CD26) enzyme activity and expression were studied in cervical cancer cells. Sitagliptin, a DPPIV/CD26 inhibitor, affected cancer cell migration and adhesion.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein regulating cell functions.
- DPVIV/CD26 plays a role in cancer processes by influencing cell proliferation, migration, and adhesion.
- Both membrane-bound and soluble forms of DPPIV/CD26 are enzymatically active.
Purpose of the Study:
- To investigate DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa, C33A) and non-tumorigenic HaCaT cells.
- To evaluate the effect of the DPPIV/CD26 inhibitor sitagliptin phosphate on cervical cancer cell migration and adhesion.
Main Methods:
- Enzymatic activity assays for DPPIV/CD26.
- DPPIV/CD26 expression analysis in cell lines.
- Cell migration and adhesion assays in the presence and absence of sitagliptin phosphate.
Main Results:
- Cervical cancer cells and keratinocytes showed DPPIV/CD26 enzymatic activity in both membrane-bound and soluble forms.
- DPPIV/CD26 expression was detected in HaCaT, SiHa, and C33A cells, but was nearly undetectable in HeLa cells.
- Sitagliptin increased migration in SiHa cells, suggesting DPPIV/CD26 regulates migration.
- Sitagliptin significantly reduced adhesion in SiHa and HeLa cells, independent of DPPIV/CD26.
Conclusions:
- This study is the first to report DPPIV/CD26 activity and expression in cervical cancer cells.
- DPPIV/CD26 activity influences cervical cancer cell migration.
- Sitagliptin's effect on cell adhesion appears to be independent of DPPIV/CD26 in these cell lines.
