PMID- 29535824
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 12
DP  - 2018 Feb 13
TI  - HIF-1 maintains a functional relationship between pancreatic cancer cells and 
      stromal fibroblasts by upregulating expression and secretion of Sonic hedgehog.
PG  - 10525-10535
LID - 10.18632/oncotarget.24156 [doi]
AB  - Hypoxic and stroma-rich microenvironments, characteristic features of pancreatic 
      cancers, are strongly associated with a poor prognosis. However, whether and how 
      hypoxia increases stromal compartments remain largely unknown. Here, we 
      investigated the potential importance of a master regulator of the cellular 
      adaptive response to hypoxia, hypoxia-inducible factor-1 (HIF-1), in the 
      formation of stroma-rich microenvironments of pancreatic tumors. We found that 
      pancreatic cancer cells secreted more Sonic hedgehog protein (SHH) under hypoxia 
      by upregulating its expression and efficiency of secretion in a HIF-1-dependent 
      manner. Recombinant SHH, which was confirmed to activate the hedgehog signaling 
      pathway, accelerated the growth of fibroblasts in a dose-dependent manner. The 
      SHH protein secreted from pancreatic cancer cells under hypoxic conditions 
      promoted the growth of fibroblasts by stimulating their Sonic hedgehog signaling 
      pathway. These results suggest that the increased secretion of SHH by HIF-1 is 
      potentially responsible for the formation of detrimental and stroma-rich 
      microenvironments in pancreatic cancers, therefore providing a rational basis to 
      target it in cancer therapy.
FAU - Katagiri, Tomohiro
AU  - Katagiri T
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
FAU - Kobayashi, Minoru
AU  - Kobayashi M
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
AD  - Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation 
      Biology Center, Kyoto University, Yoshida Konoe-Cho, Sakyo-Ku, Kyoto 606-8501, 
      Japan.
FAU - Yoshimura, Michio
AU  - Yoshimura M
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
FAU - Morinibu, Akiyo
AU  - Morinibu A
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
AD  - Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation 
      Biology Center, Kyoto University, Yoshida Konoe-Cho, Sakyo-Ku, Kyoto 606-8501, 
      Japan.
FAU - Itasaka, Satoshi
AU  - Itasaka S
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
FAU - Hiraoka, Masahiro
AU  - Hiraoka M
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
FAU - Harada, Hiroshi
AU  - Harada H
AD  - Department of Radiation Oncology and Image-Applied Therapy, Kyoto University 
      Graduate School of Medicine, Sakyo-Ku, Kyoto 606-8507, Japan.
AD  - Laboratory of Cancer Cell Biology, Department of Genome Dynamics, Radiation 
      Biology Center, Kyoto University, Yoshida Konoe-Cho, Sakyo-Ku, Kyoto 606-8501, 
      Japan.
AD  - Precursory Research for Embryonic Science and Technology, Japan Science and 
      Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180111
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5828220
OTO - NOTNLM
OT  - Sonic hedgehog signaling pathway
OT  - hypoxia-inducible factor 1 (HIF-1)
OT  - pancreatic cancers
OT  - stromal fibroblasts
OT  - tumor hypoxia
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/03/15 06:00
MHDA- 2018/03/15 06:01
PMCR- 2018/02/13
CRDT- 2018/03/15 06:00
PHST- 2016/11/07 00:00 [received]
PHST- 2018/01/04 00:00 [accepted]
PHST- 2018/03/15 06:00 [entrez]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2018/03/15 06:01 [medline]
PHST- 2018/02/13 00:00 [pmc-release]
AID - 24156 [pii]
AID - 10.18632/oncotarget.24156 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jan 11;9(12):10525-10535. doi: 10.18632/oncotarget.24156. 
      eCollection 2018 Feb 13.