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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 hyperglycemia on the expression of E-cadherin, N-cadherin, vimentin, and snail in nude mice. Immunohistochemistry was performed to compare the expression of E-cadherin, N-cadherin, vimentin, and snail in the orthotopic nude mice between euglycemia group and hyperglycemia group. ∗P < 0.05 as compared with the euglycemia group. Original magnification ×400.
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fig5: Effect of hyperglycemia on the expression of E-cadherin, N-cadherin, vimentin, and snail in nude mice. Immunohistochemistry was performed to compare the expression of E-cadherin, N-cadherin, vimentin, and snail in the orthotopic nude mice between euglycemia group and hyperglycemia group. ∗P < 0.05 as compared with the euglycemia group. Original magnification ×400.

Mentions: To further confirm whether hyperglycemia could induce EMT in PC, we examined the expression of EMT markers in the tumor tissue using immunohistochemical staining. As illustrated in Figure 5, the expression of E-cadherin was located in cell membrane, whereas N-cadherin, vimentin, and snail were mainly localized in cytoplasm. The E-cadherin staining of tumor cells was stronger in the euglycemia group than that in the hyperglycemia group, indicating that hyperglycemia was able to decrease the expression of E-cadherin. The percentage of cancer area with positive E-cadherin staining cancer cells was higher in the euglycemia group than that in the hyperglycemia group. In contrast, the N-cadherin, vimentin, and snail staining in the cytoplasm of the cancer cells was significantly stronger in the hyperglycemia group than that in the euglycemia group.


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 hyperglycemia on the expression of E-cadherin, N-cadherin, vimentin, and snail in nude mice. Immunohistochemistry was performed to compare the expression of E-cadherin, N-cadherin, vimentin, and snail in the orthotopic nude mice between euglycemia group and hyperglycemia group. ∗P < 0.05 as compared with the euglycemia group. Original magnification ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Effect of hyperglycemia on the expression of E-cadherin, N-cadherin, vimentin, and snail in nude mice. Immunohistochemistry was performed to compare the expression of E-cadherin, N-cadherin, vimentin, and snail in the orthotopic nude mice between euglycemia group and hyperglycemia group. ∗P < 0.05 as compared with the euglycemia group. Original magnification ×400.
Mentions: To further confirm whether hyperglycemia could induce EMT in PC, we examined the expression of EMT markers in the tumor tissue using immunohistochemical staining. As illustrated in Figure 5, the expression of E-cadherin was located in cell membrane, whereas N-cadherin, vimentin, and snail were mainly localized in cytoplasm. The E-cadherin staining of tumor cells was stronger in the euglycemia group than that in the hyperglycemia group, indicating that hyperglycemia was able to decrease the expression of E-cadherin. The percentage of cancer area with positive E-cadherin staining cancer cells was higher in the euglycemia group than that in the hyperglycemia group. In contrast, the N-cadherin, vimentin, and snail staining in the cytoplasm of the cancer cells was significantly stronger in the hyperglycemia group than that in the euglycemia group.

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