Published in:
Open Access
01-12-2014 | Research
Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of β-cell
Authors:
Langping Tan, Xiao Ye, Yu Zhou, Min Yu, Zhiqiang Fu, Ruiwan Chen, Baoxiong Zhuang, Bing Zeng, Huilin Ye, Wenchao Gao, Qing Lin, Zhihua Li, Quanbo Zhou, Rufu Chen
Published in:
Journal of Translational Medicine
|
Issue 1/2014
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Abstract
Background
Understanding the pathogenic mechanism of pancreatic cancer associated diabetes (PCDM) might help yield biomarkers for the early diagnosis of pancreatic cancer (PC) from population with new-onset diabetes. In the current study, we sought to determine the role of macrophage migration inhibitory factor (MIF) in PCDM pathogenesis.
Methods
The protein and mRNA levels of MIF in paraffin-embedded human PC samples, chronic pancreatitis specimens, and normal pancreas were measured by immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction. We measured serum levels of MIF in PC patients and controls. The biologic impacts of MIF overexpression on insulin secretion function of mice islets and β cells (HIT-T15) were investigated in vitro.
Results
MIF expression was significantly increased in pancreatic cancer tissues compared with chronic pancreatitis or normal pancreas specimens. The insulin secretion function of both islets and HIT-T15 cells was impaired by indirect co-cultured with PC cells or treated with conditioned media from them. Stable MIF knock-down significantly decreased the diabetogenic effect of PC cells, while MIF knock-in HPDE6 cells demonstrated a strong inhibitory effect on insulin secretion function of islets and HIT-T15 cells. MIF impaired βcell function by depressing the Ca2+ currents, decreasing L-type Ca2+ channel α1 subunit protein expression level, and enhancing p-Src activity. Mean serum level of MIF was significant higher in new-onset diabetes associated PC patients in comparison with other groups.
Conclusions
MIF is up-regulated in patients with pancreatic cancer and causes dysfunction of insulin secretion in β-cells.