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.

Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer

“…CD26 has been reported to be secreted in the serum of patients with different cancer types and therefore it has been proposed as a potential tumour biomarker www.nature.com/scientificreports www.nature.com/scientificreports/ of diagnostic and prognostic value in a wide range of cancers including pancreatic cancer [40][41][42] . CD26 has also been suggested as a cancer stem cell marker in different types of cancer and a potential therapeutic target [43][44][45] .…”

Characterization of Phloroglucinol‐enriched Fractions of Brazilian Hypericum Species and Evaluation of Their Effect on Human Keratinocytes Proliferation

“…Three independent experiments were performed in quintuplicate for each test. Results were expressed as percentage of cell proliferation, where cells treated with only DMEM/10% FBS were considered as 100% of cell viability (Beckenkamp et al, ).…”

“…DMEM/10% FBS was added, the suspension of cells were diluted with Trypan blue (1:1 v / v ) to selectively stain dead cells, and viable cells (Trypan blue negative) were counted immediately by Neubauer chamber in an optical microscope (Olympus, CX21 model, Tokyo, Japan). The results were expressed compared with control (DMEM/10% FBS) that represented 100% of viability (Beckenkamp et al, ).…”

“…Wound closure into the scratched region was recorded using an Olympus IX71 microscopy system coupled to an Olympus DP73 digital camera at 0 and 24 h after treatment. Results were calculated by comparing the wound closure after 24 h with the initial time (Beckenkamp et al, ).…”

The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease

“…Information on the role of DPP-4/CD26 in tumor biology can be inferred from either transgenic animals that lack DPP-4 or its pharmacological inhibition. Moreover, studies that assessed the depletion or absence of DDP4 have been conducted in cervical cancer [46], colorectal cancer (CRC) [47], melanoma [48], and lung tumor models [49] . Metastasis and tumor invasion are dependent upon matrix degradation, which allows cell mobility and tissue penetration.…”