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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

The metastasis of pancreatic tumor in nude mice. Metastatic Panc-1 tumors were analyzed by hematoxylin-eosin staining. (a) Ascites generation; (b) pancreatic tumor; (c) liver metastatic tumor; (d) spleen metastatic tumor. Original magnification ×400.
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fig4: The metastasis of pancreatic tumor in nude mice. Metastatic Panc-1 tumors were analyzed by hematoxylin-eosin staining. (a) Ascites generation; (b) pancreatic tumor; (c) liver metastatic tumor; (d) spleen metastatic tumor. Original magnification ×400.

Mentions: To determine whether hyperglycemic condition and H2O2 were involved in PC metastasis, equal numbers (1 × 108) of Panc-1 cells were injected into the body of mice pancreas (both euglycemic mice and hyperglycemic mice). 3 days later, a dose of 1000 units/d PEG-CAT was intraperitoneally injected into nude mice. Eight weeks after injection of the cells, mice were sacrificed and the metastatic tumors were recorded (Figure 4). As described in Table 1, only one out of six euglycemic animals generated ascites, whereas five out of six hyperglycemic mice generated ascites. Two mice in the hyperglycemia + PEG-CAT group produced ascites. In addition, none of the euglycemic mice developed visible liver metastasis, whereas four out of six hyperglycemic mice developed liver metastasis. After injected PEG-CAT, only one hyperglycemic mouse developed liver metastasis. Taken together, these results show that the number of mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. PEG-CAT injection might reverse these effects. The hyperglycemia-induced level of H2O2 might be involved in the acceleration of tumor metastasis.


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)

The metastasis of pancreatic tumor in nude mice. Metastatic Panc-1 tumors were analyzed by hematoxylin-eosin staining. (a) Ascites generation; (b) pancreatic tumor; (c) liver metastatic tumor; (d) spleen metastatic tumor. Original magnification ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: The metastasis of pancreatic tumor in nude mice. Metastatic Panc-1 tumors were analyzed by hematoxylin-eosin staining. (a) Ascites generation; (b) pancreatic tumor; (c) liver metastatic tumor; (d) spleen metastatic tumor. Original magnification ×400.
Mentions: To determine whether hyperglycemic condition and H2O2 were involved in PC metastasis, equal numbers (1 × 108) of Panc-1 cells were injected into the body of mice pancreas (both euglycemic mice and hyperglycemic mice). 3 days later, a dose of 1000 units/d PEG-CAT was intraperitoneally injected into nude mice. Eight weeks after injection of the cells, mice were sacrificed and the metastatic tumors were recorded (Figure 4). As described in Table 1, only one out of six euglycemic animals generated ascites, whereas five out of six hyperglycemic mice generated ascites. Two mice in the hyperglycemia + PEG-CAT group produced ascites. In addition, none of the euglycemic mice developed visible liver metastasis, whereas four out of six hyperglycemic mice developed liver metastasis. After injected PEG-CAT, only one hyperglycemic mouse developed liver metastasis. Taken together, these results show that the number of mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. PEG-CAT injection might reverse these effects. The hyperglycemia-induced level of H2O2 might be involved in the acceleration of tumor metastasis.

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