Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling

Yoshihiro Morifuji, Hideya Ohnishi, Hironori Iwasaki, Akira Imaizumi, kenji nakano, Masao Tanaka, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly types of malignancies because of its high ability to metastasize. PDAC is thought to be under hypoxic condition. Therefore, to investigate the mechanism of metastatic processes, chronic-hypoxia-resistant PDAC cells were newly generated under hypoxic condition for 3-6 months and reoxygenation experiments were performed using these chronic-hypoxia-resistant PDAC cells in in vivo-mimicking conditions. Proliferation, invasiveness and tumorigenicity in PDAC cells were significantly increased by reoxygenation. A Hedgehog (Hh) signaling component, Gli1, was significantly increased by reoxygenation. Gli1 knockdown inhibited reoxygenation-induced increases in proliferation and tumorigenicity and decreased invasiveness through suppression of matrix metalloproteinase (MMP) 2 and MMP9. Moreover, inhibition of Sonic Hh and Smoothened abrogated reoxygenation induced increases in proliferation and invasiveness. These results suggest that metastatic processes in PDAC are induced through activation of the Hh signaling pathway. Therefore, the Hh signaling pathway may be a therapeutic target for refractory PDAC in metastatic processes induced by reoxygenation.

元の言語英語
ページ(範囲)324-333
ページ数10
ジャーナルCancer Science
105
発行部数3
DOI
出版物ステータス出版済み - 1 1 2014

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Pancreatic Neoplasms
Adenocarcinoma
Matrix Metalloproteinase 2
Hypoxia
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling. / Morifuji, Yoshihiro; Ohnishi, Hideya; Iwasaki, Hironori; Imaizumi, Akira; nakano, kenji; Tanaka, Masao; Katano, Mitsuo.

:: Cancer Science, 巻 105, 番号 3, 01.01.2014, p. 324-333.

研究成果: ジャーナルへの寄稿記事

Morifuji, Yoshihiro ; Ohnishi, Hideya ; Iwasaki, Hironori ; Imaizumi, Akira ; nakano, kenji ; Tanaka, Masao ; Katano, Mitsuo. / Reoxygenation from chronic hypoxia promotes metastatic processes in pancreatic cancer through the Hedgehog signaling. :: Cancer Science. 2014 ; 巻 105, 番号 3. pp. 324-333.
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AU - Ohnishi, Hideya

AU - Iwasaki, Hironori

AU - Imaizumi, Akira

AU - nakano, kenji

AU - Tanaka, Masao

AU - Katano, Mitsuo

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