Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells.
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Our previous study demonstrated a possible link between DPPIV expression and decreased i.p. dissemination and loss of invasive potential of ovarian carcinoma. In this report, we examined the mechanisms of the anti-invasive ability of DPPIV in greater detail. Expression of E-cadherin and beta-catenin was positively correlated with DPPIV expression among five independent ovarian carcinoma cell lines. The introduction of DPPIV cDNA into an ovarian carcinoma cell line (SKOV3) with low DPPIV expression enhanced the expression of E-cadherin and beta-catenin, with a cellular morphological change from a fibroblastic and motile phenotype to an epithelial phenotype. In addition, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. In contrast, tissue inhibitors of matrix metalloproteinases were up-regulated by DPPIV transfection. Furthermore, suppression of the phosphorylation levels of mitogen-activated protein kinase isoform, extracellular signal-regulated kinase, was observed in DPPIV-overexpressing cells. To our knowledge, this is the first evidence that increasing DPPIV expression may contribute to prolonged survival by up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases.
Kajiyama
Hiroaki
H
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Japan.
Kikkawa
Fumitaka
F
Khin
EiEi
E
Shibata
Kiyosumi
K
Ino
Kazuhiko
K
Mizutani
Shigehiko
S
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015820:Cadherins; D019714:Tissue Inhibitor of Metalloproteinases; D018819:Dipeptidyl Peptidase 4; D020782:Matrix Metalloproteinases