The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells.
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Recent studies have suggested that DPPIV plays an important role in tumor progression in several human malignancies. In the current study, we investigated the role of DPPIV in paclitaxel resistance in epithelial ovarian carcinoma (EOC) cells. We first examined the correlation between expression levels of DPPIV and sensitivity to paclitaxel in various EOC cell lines. Subsequently, to clarify the cellular functions of DPPIV, we investigated the role of this molecule in the sensitivity of EOC to paclitaxel in vitro and in vivo using stably DPPIV-transfected EOC cells. We identified a positive correlation between DPPIV expression and paclitaxel sensitivity in various EOC cell lines. In addition, we observed a significant increase in the paclitaxel sensitivity of DPPIV-overexpressing EOC cells. Furthermore, no apparent alteration in paclitaxel sensitivity was noted by the addition of a specific inhibitor of DPPIV activity in DPPIV-transfected or natively DPPIV-overexpressing EOC cells. In a subcutaneous murine model treated with paclitaxel, on Day 39, the tumor size of the DPPIV-transfected cell-inoculated group was as large as that of the vector-transfected cell-inoculated group. In contrast, on Day 61, the former was smaller than the latter. The present findings show that DPPIV may be involved in the increased sensitivity to paclitaxel of EOC cells regardless of the involvement of DPPIV activity.
Kajiyama
Hiroaki
H
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kajiyama@med.nagoya-u.ac.jp
Shibata
Kiyosumi
K
Ino
Kazuhiko
K
Mizutani
Shigehiko
S
Nawa
Akihiro
A
Kikkawa
Fumitaka
F
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000502:physiology*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005260:Female; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D054873:Dipeptidyl-Peptidase IV Inhibitors; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D017239:Paclitaxel