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IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells

Year: 2007
Type: article
Abstract: BACKGROUND: Although upregulation of interleukin-6 (IL-6) is associated with many solid tumors, its role in pancreatic cancer has not been well elucidated. In this study, we examined the expression of IL-6 in pancreatic cancer cells, and determined the effect of exogenous IL-6 on cytokine secretion, gene expression and signaling in human pancreatic cancer cells. METHODS: The mRNA levels of IL-6, VEGF165, neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2) were determined by real-time RT PCR. Phosphorylation of ERK2 in pancreatic cancer cells was determined by using Bio-Plex phosphoprotein assay. The expression of IL-6 and other cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay. RESULTS: Pancreatic cancer cell lines expressed higher levels of IL-6 than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous IL-6 increased the secretion of multiple Th2 type of cytokines in Panc-1, MIA PaCa-2 and BxPC-3 cells. IL-6 also upregulated the expression of VEGF165, and NRP-1, and both IL-6 and VEGF165 were inducible by hypoxia. In addition, IL-6 activated ERK2 signaling pathways in pancreatic cancer cells. CONCLUSIONS: IL-6 may be involved in promoting human pancreatic cancer develop ment by furnishing Th2 type of cytokine environment and upregulating cell proliferation and angiogenesis related genes. Targeting IL-6 might be an effective treatment for pancreatic cancer.
DOI: 10.4161/cbt.6.7.4328
Authors: Louis W. Feurino, Yuqing Zhang, Uddalak Bharadwaj, Rongxin Zhang, Fei Li, William E. Fisher, F. Charles Brunicardi, Changyi Chen, Qizhi Yao, Min Li
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: bronze
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Institute of Dental and Craniofacial Research, National Center for Complementary and Integrative Health
Awards: G1821703018, HIV PROTEASE INHIBITORS EFFECT--NENDOTHELIAL DYSFUNCTION, TARGETED MUTAGENESIS OF NEUROENDOCRINE REGULATORY GENES, Role of Somatostatin Receptors in Pancreatic Cancer, Effects of HIV Protease Inhibitors of Endothelial Barrie, Tissue engineering of small diameter vascular graft, Influenza HA in SHIV VLPS for mucosal vaccination, Ginkgo Biloba Enhances Therapeutic HIV Vaccination, G6170213943, G6217743226, G640625107, G675304304, G8511460556
OpenAlex ID: W1973533486
FWCI: 2.523
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Cited by: 115
Related to: 10