PT  - JOURNAL ARTICLE
AU  - Yi-Ting Chen
AU  - Tso-Wen Wang
AU  - Tsung-Hao Chang
AU  - Teng-Po Hsu
AU  - Jhih-Ying Chi
AU  - Yu-Wei Hsiao
AU  - Chien-Feng Li
AU  - Ju-Ming Wang
TI  - HDGF supports anti-apoptosis and pro-fibrosis in pancreatic stellate cells of pancreatic cancer
AID  - 10.1101/272542
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 272542
4099  - http://biorxiv.org/content/early/2018/11/06/272542.short
4100  - http://biorxiv.org/content/early/2018/11/06/272542.full
AB  - 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.