IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells.
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.
Feurino
Louis W
LW
Molecular Surgeon Research Center, Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medidcine, Houston, Texas 77030, USA.
Zhang
Yuqing
Y
Bharadwaj
Uddalak
U
Zhang
Rongxin
R
Li
Fei
F
Fisher
William E
WE
Brunicardi
F Charles
FC
Chen
Changyi
C
Yao
Qizhi
Q
Min
L
L
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D039942:Neuropilin-1 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D048049:Extracellular Signal-Regulated MAP Kinases