Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma.
Int J Mol Sci
; 17(6)2016 Jun 03.
Article
in En
| MEDLINE
| ID: mdl-27271610
ABSTRACT
Hypoxia inducible factor 1 (HIF-1) is a transcription factor composed of two subunits, namely, HIF-1α and HIF-1ß, in which HIF-1ß is constitutively expressed. HIF-1 upregulates several hypoxia-responsive proteins, including angiogenesis factors, glycolysis solution enzymes, and cell survival proteins. HIF-1 is also associated with the degree of inflammation in the tumor region, but the exact mechanism remains unclear. This study aims to identify the molecular mechanism of recruiting monocytes/macrophages by HIF-1α in pancreatic ductal adenocarcinoma (PDAC) and the effects of macrophages on pancreatic stellate cells (PSCs). Immunohistochemistry (IHC) was performed for cluster of differentiation 68 (CD68), HIF-1α, and chemical chemokines 2 (CCL2). Western blot, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation assay, and The Cancer Genome Atlas (TCGA) were used to verify the correlation between HIF-1α and CCL2 at protein and nucleic acid levels. Monocytes/macrophages were co-cultured with PSCs to observe their interaction. Samples showed significant correlation between CD68 and HIF-1α (t-test, p < 0.05). HIF-1α recruited monocytes/macrophages by promoting CCL2 secretion. Moreover, macrophages could accelerate the activation of PSCs. HIF-1α might promote inflammation and fibrosis of PDAC through CCL2 secretion, which may provide a novel target to treat PDAC patients.
Key words
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Carcinoma, Pancreatic Ductal
/
Hypoxia-Inducible Factor 1
/
Pancreatic Stellate Cells
/
Macrophages
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2016
Document type:
Article