Total for the last 12 months
number of access : ?
number of downloads : ?
ID 114899
Title Alternative
Podoplanin promotes progression of MPM
Author
Takeuchi, Shinji Kanazawa University
Fukuda, Koji Kanazawa University
Yamada, Tadaaki Kanazawa University
Arai, Sachiko Kanazawa University
Takagi, Satoshi Japanese Foundation for Cancer Research
Ishii, Genichiro National Cancer Center Hospital East
Ochiai, Atsushi National Cancer Center Hospital East
Iwakiri, Shotaro Hyogo Prefectural Amagasaki General Medical Center
Itoi, Kazumi Hyogo Prefectural Amagasaki General Medical Center
Nishihara, Hiroshi Hokkaido University
Fujita, Naoya Japanese Foundation for Cancer Research
Yano, Seiji Kanazawa University
Keywords
focus formation
mesothelioma
motility
podoplanin
YAP1
Content Type
Journal Article
Description
Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility. In contrast, overexpression of PDPN in PDPN-low expressing MPM cells enhanced cell motility. PDPN stimulated motility was mediated by activation of the RhoA/ROCK pathway. Moreover, knocking down PDPN with short hairpin (sh) RNA in PDPN-high expressing MPM cells resulted in decreased development of a thoracic tumor in mice with severe combined immune deficiency (SCID). In sharp contrast, transfection of PDPN in PDPN-low expressing MPM cells resulted in an increase in the number of Ki-67-positive proliferating tumor cells and it promoted progression of a thoracic tumor in SCID mice. Interestingly, PDPN promoted focus formation in vitro, and a low level of E-cadherin expression and YAP1 activation was observed in PDPN-high MPM tumors. These findings indicate that PDPN is a diagnostic marker as well as a pathogenetic regulator that promotes MPM progression by increasing cell motility and inducing focus formation. Therefore, PDPN might be a pathogenetic determinant of MPM dissemination and aggressive growth and may thus be an ideal therapeutic target.
Journal Title
Cancer Science
ISSN
13497006
Publisher
Japanese Cancer Association|John Wiley & Sons
Volume
108
Issue
4
Start Page
696
End Page
703
Published Date
2017-02-09
Rights
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License(https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital