Abstract
We previously showed that an inflammation-related, molecule leucine-rich alpha-2 glycoprotein (LRG) enhances the transforming growth factor (TGF)-β1-induced phosphorylation of Smad proteins and is elevated in patients with pancreatic ductal adenocarcinoma (PDAC). As TGF-β/Smad signaling is considered to play a key role in epithelial-mesenchymal transition (EMT), we attempted to clarify the mechanism underlying LRG-related EMT in relation to metastasis in PDAC. We cultured LRG-overexpressing PDAC cells (Panc1/LRG) and evaluated the morphology, EMT-related molecules and TGF-β/Smad signaling pathway in these cells. We also assessed the LRG levels in plasma and resected specimens from patients with PDAC. Inflammatory cytokines induced LRG production in PDAC cells. A spindle-like shape was visualized more frequently than other shapes in Panc1/LRG with TGF-β1 exposure. The expression of E-cadherin in Panc1/LRG was decreased with TGF-β1 exposure. Invasion increased with TGF-β1 stimulation of Panc1/LRG. The phosphorylation of smad2 in Panc1/LRG was increased in comparison with parental Panc1 under TGF-β1 stimulation. In the plasma LRG-high group, the recurrence rate tended to be higher and the recurrence-free survival (RFS) tended to be worse in comparison with the plasma LRG-low group. LRG enhanced EMT induced by TGF-β signaling, thus indicating that LRG has a significant effect on the metastasis of PDAC.
| Original language | English |
|---|---|
| Pages (from-to) | 985-996 |
| Number of pages | 12 |
| Journal | Cancer Science |
| Volume | 110 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Epithelial-mesenchymal transition via transforming growth factor beta in pancreatic cancer is potentiated by the inflammatory glycoprotein leucine-rich alpha-2 glycoprotein. / Otsuru, Toru; Kobayashi, Shogo; Wada, Hiroshi; Takahashi, Tsuyoshi; Gotoh, Kunihito; Iwagami, Yoshifumi; Yamada, Daisaku; Noda, Takehiro; Asaoka, Tadafumi; Serada, Satoshi; Fujimoto, Minoru; Eguchi, Hidetoshi; Mori, Masaki; Doki, Yuichiro; Naka, Testuji.
In: Cancer Science, Vol. 110, No. 3, 03.2019, p. 985-996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epithelial-mesenchymal transition via transforming growth factor beta in pancreatic cancer is potentiated by the inflammatory glycoprotein leucine-rich alpha-2 glycoprotein
AU - Otsuru, Toru
AU - Kobayashi, Shogo
AU - Wada, Hiroshi
AU - Takahashi, Tsuyoshi
AU - Gotoh, Kunihito
AU - Iwagami, Yoshifumi
AU - Yamada, Daisaku
AU - Noda, Takehiro
AU - Asaoka, Tadafumi
AU - Serada, Satoshi
AU - Fujimoto, Minoru
AU - Eguchi, Hidetoshi
AU - Mori, Masaki
AU - Doki, Yuichiro
AU - Naka, Testuji
PY - 2019/3
Y1 - 2019/3
N2 - We previously showed that an inflammation-related, molecule leucine-rich alpha-2 glycoprotein (LRG) enhances the transforming growth factor (TGF)-β1-induced phosphorylation of Smad proteins and is elevated in patients with pancreatic ductal adenocarcinoma (PDAC). As TGF-β/Smad signaling is considered to play a key role in epithelial-mesenchymal transition (EMT), we attempted to clarify the mechanism underlying LRG-related EMT in relation to metastasis in PDAC. We cultured LRG-overexpressing PDAC cells (Panc1/LRG) and evaluated the morphology, EMT-related molecules and TGF-β/Smad signaling pathway in these cells. We also assessed the LRG levels in plasma and resected specimens from patients with PDAC. Inflammatory cytokines induced LRG production in PDAC cells. A spindle-like shape was visualized more frequently than other shapes in Panc1/LRG with TGF-β1 exposure. The expression of E-cadherin in Panc1/LRG was decreased with TGF-β1 exposure. Invasion increased with TGF-β1 stimulation of Panc1/LRG. The phosphorylation of smad2 in Panc1/LRG was increased in comparison with parental Panc1 under TGF-β1 stimulation. In the plasma LRG-high group, the recurrence rate tended to be higher and the recurrence-free survival (RFS) tended to be worse in comparison with the plasma LRG-low group. LRG enhanced EMT induced by TGF-β signaling, thus indicating that LRG has a significant effect on the metastasis of PDAC.
AB - We previously showed that an inflammation-related, molecule leucine-rich alpha-2 glycoprotein (LRG) enhances the transforming growth factor (TGF)-β1-induced phosphorylation of Smad proteins and is elevated in patients with pancreatic ductal adenocarcinoma (PDAC). As TGF-β/Smad signaling is considered to play a key role in epithelial-mesenchymal transition (EMT), we attempted to clarify the mechanism underlying LRG-related EMT in relation to metastasis in PDAC. We cultured LRG-overexpressing PDAC cells (Panc1/LRG) and evaluated the morphology, EMT-related molecules and TGF-β/Smad signaling pathway in these cells. We also assessed the LRG levels in plasma and resected specimens from patients with PDAC. Inflammatory cytokines induced LRG production in PDAC cells. A spindle-like shape was visualized more frequently than other shapes in Panc1/LRG with TGF-β1 exposure. The expression of E-cadherin in Panc1/LRG was decreased with TGF-β1 exposure. Invasion increased with TGF-β1 stimulation of Panc1/LRG. The phosphorylation of smad2 in Panc1/LRG was increased in comparison with parental Panc1 under TGF-β1 stimulation. In the plasma LRG-high group, the recurrence rate tended to be higher and the recurrence-free survival (RFS) tended to be worse in comparison with the plasma LRG-low group. LRG enhanced EMT induced by TGF-β signaling, thus indicating that LRG has a significant effect on the metastasis of PDAC.
UR - http://www.scopus.com/inward/record.url?scp=85061023946&partnerID=8YFLogxK
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U2 - 10.1111/cas.13918
DO - 10.1111/cas.13918
M3 - Article
C2 - 30575211
AN - SCOPUS:85061023946
VL - 110
SP - 985
EP - 996
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 3
ER -