Limits...
Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.

Li W, Zhang L, Chen X, Jiang Z, Zong L, Ma Q - Oxid Med Cell Longev (2016)

Bottom Line: In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased.The injection of PEG-CAT could also reverse hyperglycemia-induced EMT.These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

No MeSH data available.


Related in: MedlinePlus

Effect of the hyperglycemia/H2O2 axis on EMT in nude mice. (a) The protein levels of EMT-related factors in pancreatic tumor tissues with different serum glucose levels were analyzed using Western blotting. (b) The statistical diagram of Western blotting analysis. (c) The mRNA levels of EMT-related markers in pancreatic tumor tissues with different serum glucose levels were analyzed using qRT-PCR. ∗P < 0.05 as compared with the euglycemia group. #P < 0.05 as compared with hyperglycemia group.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4940572&req=5

fig6: Effect of the hyperglycemia/H2O2 axis on EMT in nude mice. (a) The protein levels of EMT-related factors in pancreatic tumor tissues with different serum glucose levels were analyzed using Western blotting. (b) The statistical diagram of Western blotting analysis. (c) The mRNA levels of EMT-related markers in pancreatic tumor tissues with different serum glucose levels were analyzed using qRT-PCR. ∗P < 0.05 as compared with the euglycemia group. #P < 0.05 as compared with hyperglycemia group.

Mentions: To determine whether hyperglycemia-induced EMT was H2O2-related, we analyzed the expression of E-cadherin, N-cadherin, vimentin, and snail using Western blotting analysis. As shown in Figures 6(a) and 6(b), the protein level of E-cadherin in hyperglycemia group was lower than that in the euglycemia group. The expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail was stronger in hyperglycemia group. PEG-CAT injection could reverse these hyperglycemia-induced effects. We next evaluate the effects of hyperglycemia and PEG-CAT on the expression of E-cadherin, N-cadherin, vimentin, and snail at mRNA level by qRT-PCR. As shown in Figure 6(c), PEG-CAT counterbalanced hyperglycemia-induced EMT-related factors at the mRNA level and the trend was consistent with the protein results. Taken together, our results demonstrate that hyperglycemia could induce EMT progression and facilitate tumor metastasis via the production of H2O2 in PC.


Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide.

Li W, Zhang L, Chen X, Jiang Z, Zong L, Ma Q - Oxid Med Cell Longev (2016)

Effect of the hyperglycemia/H2O2 axis on EMT in nude mice. (a) The protein levels of EMT-related factors in pancreatic tumor tissues with different serum glucose levels were analyzed using Western blotting. (b) The statistical diagram of Western blotting analysis. (c) The mRNA levels of EMT-related markers in pancreatic tumor tissues with different serum glucose levels were analyzed using qRT-PCR. ∗P < 0.05 as compared with the euglycemia group. #P < 0.05 as compared with hyperglycemia group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940572&req=5

fig6: Effect of the hyperglycemia/H2O2 axis on EMT in nude mice. (a) The protein levels of EMT-related factors in pancreatic tumor tissues with different serum glucose levels were analyzed using Western blotting. (b) The statistical diagram of Western blotting analysis. (c) The mRNA levels of EMT-related markers in pancreatic tumor tissues with different serum glucose levels were analyzed using qRT-PCR. ∗P < 0.05 as compared with the euglycemia group. #P < 0.05 as compared with hyperglycemia group.
Mentions: To determine whether hyperglycemia-induced EMT was H2O2-related, we analyzed the expression of E-cadherin, N-cadherin, vimentin, and snail using Western blotting analysis. As shown in Figures 6(a) and 6(b), the protein level of E-cadherin in hyperglycemia group was lower than that in the euglycemia group. The expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail was stronger in hyperglycemia group. PEG-CAT injection could reverse these hyperglycemia-induced effects. We next evaluate the effects of hyperglycemia and PEG-CAT on the expression of E-cadherin, N-cadherin, vimentin, and snail at mRNA level by qRT-PCR. As shown in Figure 6(c), PEG-CAT counterbalanced hyperglycemia-induced EMT-related factors at the mRNA level and the trend was consistent with the protein results. Taken together, our results demonstrate that hyperglycemia could induce EMT progression and facilitate tumor metastasis via the production of H2O2 in PC.

Bottom Line: In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased.The injection of PEG-CAT could also reverse hyperglycemia-induced EMT.These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

No MeSH data available.


Related in: MedlinePlus