論文

査読有り 本文へのリンクあり
2019年7月

Vasohibin-2 plays an essential role in metastasis of pancreatic ductal adenocarcinoma

Cancer Science
  • Rie Iida-Norita
  • ,
  • Minaho Kawamura
  • ,
  • Yasuhiro Suzuki
  • ,
  • Shin Hamada
  • ,
  • Atsushi Masamune
  • ,
  • Toru Furukawa
  • ,
  • Yasufumi Sato

110
7
開始ページ
2296
終了ページ
2308
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.14041

Vasohibin-2 (VASH2) is expressed in various cancers and promotes their progression. We recently reported that pancreatic cancer patients with higher VASH2 expression show poorer prognosis. Herein, we sought to characterize the role of VASH2 in pancreatic cancer. We used LSL-Kras ; LSL-Trp53 ; Pdx-1-Cre (KPC) mice, a mouse model of pancreatic ductal adenocarcinoma (PDAC), and cells isolated from them (KPC cells). Knockdown of Vash2 from PDAC cells did not affect their proliferation, but decreased their migration. When Vash2-knockdown PDAC cells were orthotopically inoculated, liver metastasis and peritoneal dissemination were reduced, and the survival period was significantly prolonged. When KPC mice were crossed with Vash2-deficient mice, metastasis was significantly decreased in Vash2-deficient KPC mice. VASH2 was recently identified to have tubulin carboxypeptidase activity. VASH2 knockdown decreased, whereas VASH2 overexpression increased tubulin detyrosination of PDAC cells, and tubulin carboxypeptidase (TCP) inhibitor parthenolide inhibited VASH2-induced cell migration. We next clarified its role in the tumor microenvironment. Tumor angiogenesis was significantly abrogated in vivo when VASH2 was knocked down or deleted. We further examined genes downregulated by Vash2 knockdown in KPC cells, and found chemokines and cytokines that were responsible for the recruitment of myeloid derived suppressor cells (MDSC). Indeed, MDSC were accumulated in PDAC of KPC mice, and they were significantly decreased in Vash2-deficient KPC mice. These findings suggest that VASH2 plays an essential role in the metastasis of PDAC with multiple effects on both cancer cells and the tumor microenvironment, including tubulin detyrosination, tumor angiogenesis and evasion of tumor immunity. G12D R172H

リンク情報
DOI
https://doi.org/10.1111/cas.14041
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31074083
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068567045&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85068567045&origin=inward
ID情報
  • DOI : 10.1111/cas.14041
  • ISSN : 1347-9032
  • eISSN : 1349-7006
  • PubMed ID : 31074083
  • SCOPUS ID : 85068567045

エクスポート
BibTeX RIS