Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma

Hypoxia inducible factor 1 (HIF-1) is a transcription factor composed of two subunits, namely, HIF-1α and HIF-1β, in which HIF-1β 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.

• Publication year

  2016

• Venue

  International Journal of Molecular Sciences

• Publication date

  2016-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/ijms17060799PMID 27271610PMCID 4926333
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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