We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Macrophage migration inhibitory factor is overexpressed in pancreatic cancer tissues and impairs insulin secretion function of β-cell.
- Authors
Tan, Langping; Ye, Xiao; Zhou, Yu; Yu, Min; Fu, Zhiqiang; Chen, Ruiwan; Zhuang, Baoxiong; Zeng, Bing; Ye, Huilin; Gao, Wenchao; Lin, Qing; Li, Zhihua; Zhou, Quanbo; Chen, Rufu
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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 Ca⁺ currents, decreasing L-type Ca⁺ 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.<bold>Conclusions: </bold>MIF is up-regulated in patients with pancreatic cancer and causes dysfunction of insulin secretion in β-cells.
- Publication
Journal of Translational Medicine, 2014, Vol 12, Issue 1, p92
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/1479-5876-12-92