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Overexpression of interleukin-32α promotes invasion by modulating VEGF in hepatocellular carcinoma.

Abstract
Interleukin-32α (IL-32α) was reported to exhibit pluripotent pro-inflammatory properties. Recent studies indicate that it promotes the migration and invasion of cancers. We detected the expression of IL-32 in hepatocellular carcinoma (HCC) tissues and investigated its role in tumor angiogenesis and invasion. IL-32α expression in HCC was evaluated by real-time PCR, western blot analysis and immunohistochemical (IHC) staining. Secreted serum IL-32α and VEGF concentrations were detected using a custom-made sandwich ELISA. Furthermore, IL-32α was knocked down in HCC cell lines using siRNA and the cell migration and invasion abilities were assessed. IHC staining showed that IL32α-positive particles were mainly located in the cytoplasm of cancer cells, and it was significantly upregulated in the tumor tissues compared with that in peritumoral tissues. Notably, IL-32α was strongly expressed in perivascular areas. The mean serum concentration of IL-32α in HCC patients was significantly higher than that in the control group (571.45±102.28 vs. 144.60±51.172 pg/ml; P<0.01). Real-time RT-PCR showed that IL-32α mRNA was significantly overexpressed in HCC tumor tissues (IL-32/β-actin, 15.59±7.8 vs. 3.37±0.47; P<0.01). The in vitro results indicated that IL-32α knockdown inhibited the activation of VEGF-STAT3 signaling in HCC tumor cell lines. IL-32α expression was correlated with clinical relevance in HCC tumor tissues. It is strongly suggested that IL-32α may be a potential predictor of anti-angiogenesis therapy and prognosis of HCC.
AuthorsWen-Bo Zhao, Quan-Li Wang, Yan-Tian Xu, Shi-Feng Xu, Yang Qiu, Feng Zhu
JournalOncology reports (Oncol Rep) Vol. 39 Issue 3 Pg. 1155-1162 (Mar 2018) ISSN: 1791-2431 [Electronic] Greece
PMID29286122 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • IL32 protein, human
  • Interleukins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
Topics
  • Apoptosis
  • Biomarkers, Tumor (genetics, metabolism)
  • Carcinoma, Hepatocellular (genetics, metabolism, pathology)
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukins (genetics, metabolism)
  • Liver Neoplasms (genetics, metabolism, pathology)
  • Male
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic (pathology)
  • Prognosis
  • Signal Transduction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A (genetics, metabolism)

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