title: Dipeptidyl peptidase IV in tumor progression.
abstract: Dipeptidyl peptidase IV (DPPIV) is a 110-kDa glycoprotein with ubiquitous expression. Several recent studies have shown that DPPIV affects tumor progression in several human malignancies. We found that ovarian carcinoma cell lines with higher DPPIV expression showed less invasive potential. Furthermore, introduction of DPPIV cDNA into SKOV3 cells (SKDPIV), derived from serous cystadenocarcinoma showing little DPPIV expression, caused a significant decrease in both migration and invasive potential. In addition, nude mice inoculated with SKDPIV cells showed significantly less peritoneal dissemination and longer survival time than those inoculated with parental or vector-transfected cells. We further examined the mechanisms of anti-invasive ability of DPPIV. The expression of E-cadherin was positively correlated with DPPIV expression among five independent ovarian carcinoma cell lines. The SKDPIV cells showed enhanced expression of E-cadherin with a cellular morphological change from a fibroblastic and motile phenotype to an epithelial phenotype compared to parental and MOCK cells. In addition, matrix metalloproteinase 2 (MMP-2) and membrane type 1 matrix metalloprotease (MT1-MMP), which are important markers associated with invasive and metastatic potential, were remarkably reduced in SKDPIV cells. In contrast, tissue inhibitors of matrix metalloproteinases (TIMPs) were enhanced by DPPIV transfection. These findings imply that DPPIV may functionally suppress peritoneal dissemination and progression of ovarian carcinoma by regulating the expression levels of several molecules associated with carcinoma cell invasion and progression.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan. kikkawaf@med.nagoya-u.ac.jp
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ino
authors.forename: Seiji
authors.initials: S
authors.lastname: Nomura
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Mizutani
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014162:Transfection
chemical_list: D015820:Cadherins; D018819:Dipeptidyl Peptidase 4