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HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer

Yi-Ting Chen, View ORCID ProfileTso-Wen Wang, Tsung-Hao Chang, Teng-Po Hsu, Jhih-Ying Chi, Yu-Wei Hsiao, Chien-Feng Li, Ju-Ming Wang
doi: https://doi.org/10.1101/272542
Yi-Ting Chen
1Medical Research Department, Chi Mei Medical Center, Tainan, Taiwan.
2Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
3Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
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Tso-Wen Wang
3Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
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  • ORCID record for Tso-Wen Wang
Tsung-Hao Chang
4Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Teng-Po Hsu
5Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
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Jhih-Ying Chi
4Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Yu-Wei Hsiao
3Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
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Chien-Feng Li
6Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.
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  • For correspondence: angelo.p@yahoo.com.tw
Ju-Ming Wang
2Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
3Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
7Interbational Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
8Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
9Graduate Institute of Medical, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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  • For correspondence: angelo.p@yahoo.com.tw
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ABSTRACT

Pancreatic cancer is refractory and characterized by extensively surrounding- and intra-tumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Activation of PSCs plays a pivotal role for developing fibrotic reactions to affect themselves or pancreatic cancer cells (PCCs). In the current study, we demonstrated that hepatoma-derived growth factor (HDGF) was secreted from transforming growth factor-β1 (TGF-β1)-treated PSCs. We found that HDGF contributed to anti-apoptosis of PSCs and led to synthesis and depositions of extracellular matrix proteins for stabilizing PSCs/PCCs tumor foci. CCAAT/enhancer binding protein δ (CEBPD) responds to TGF-β1 through a reciprocal loop regulation and further activated hypoxia inducible factor-1α (HIF-1α) contributed to up-regulation of HDGF gene. It agrees with the observation that severe stromal growth positively correlated with stromal HDGF and CEBPD in pancreatic cancer specimens. Collectively, the identification of TGF-β1-activated CEBPD/HIF-1α/HDGF axis provides new insights for the novel discoveries of HDGF in anti-apoptosis and pro-fibrosis of PSCs and outgrowth of pancreatic cancer cells.

Footnotes

  • Funding:This work was financially supported by the National Science Council Grant (NHRI-EX106-10422BI from the National Health Research Institute and MOST 106-2320-B-006-063-MY3 from the Ministry of Science and Technology) and Chi Mei Medical Center Research Grant #10501.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 06, 2018.
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HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer
Yi-Ting Chen, Tso-Wen Wang, Tsung-Hao Chang, Teng-Po Hsu, Jhih-Ying Chi, Yu-Wei Hsiao, Chien-Feng Li, Ju-Ming Wang
bioRxiv 272542; doi: https://doi.org/10.1101/272542
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HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer
Yi-Ting Chen, Tso-Wen Wang, Tsung-Hao Chang, Teng-Po Hsu, Jhih-Ying Chi, Yu-Wei Hsiao, Chien-Feng Li, Ju-Ming Wang
bioRxiv 272542; doi: https://doi.org/10.1101/272542

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