In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 212, No. 3 ( 2015-03-09), p. 333-349
Abstract:
Pancreatic cancer has an extremely high mortality rate due to its aggressive metastatic nature. Resolving the underlying mechanisms will be crucial for treatment. Here, we found that overexpression of IL-17B receptor (IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Consistently, results from ex vivo experiments further validated that IL-17RB and its ligand, IL-17B, plays an essential role in pancreatic cancer metastasis and malignancy. Signals from IL-17B–IL-17RB activated CCL20/CXCL1/IL-8/TFF1 chemokine expressions via the ERK1/2 pathway to promote cancer cell invasion, macrophage and endothelial cell recruitment at primary sites, and cancer cell survival at distant organs. Treatment with a newly derived monoclonal antibody against IL-17RB blocked tumor metastasis and promoted survival in a mouse xenograft model. These findings not only illustrate a key mechanism underlying the highly aggressive characteristics of pancreatic cancer but also provide a practical approach to tackle this disease.
Type of Medium:
Online Resource
ISSN:
1540-9538
,
0022-1007
DOI:
10.1084/jem.20141702
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2015
detail.hit.zdb_id:
1477240-1