Pancreatic cancer is considered largely incurable, even when diagnosed at an early stage. Due to a lack of early symptoms and the aggressive nature of pancreatic tumors, pancreatic cancer patients are often diagnosed at late stage, when metastasis has already occurred. The poor prognosis of pancreatic cancer has been mainly attributed to its aggressive local invasion and early metastasis.
Researchers from Taiwan have discovered that overexpression of IL-17B receptor(IL-17RB) strongly correlated with postoperative metastasis and inversely correlated with progression-free survival in pancreatic cancer patients. Their study was published in JEM.
IL-17RB has been detected in kidney, pancreas, liver, brain, and intestine, and up-regulation of IL-17RB expression was found in intestinal inflammation. Overexpression was associated with poor breast cancer prognosis. Depletion of IL-17RB resulted in reduction of tumorigenic ability of breast cancer cells. It is likely that IL-17B-IL-17RB autocrine signaling may contribute to the malignant nature of pancreatic cancer.
In this study, researchers found that IL-17B/RB signaling is essential for pancreatic cancer malignancy. IL-17B-IL-17RB signal pathway enhanced tumor malignancy through two distinct pathways. One was to activate IL-8 expression via transcription factors nuclear factor κB(NF- κB) and activator protein-1 (AP-1) to promote incasion and vasculogenic endothelial cell recruitment. Importantly, treatment with a newly developed monoclonal antibody against IL-17RB blocked tumor growth and metastasis, and also promoted survival in a mouse xenograft model.
These findings shed light on the underlying mechanism of pancreatic cancer malignancy and provide a promising therapeutic target to inhibit pancreatic cancer progression.
Reference:
Wu H H, Hwang-Verslues W W, Lee W H, et al. Targeting IL-17B–IL-17RB signaling with an anti–IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines[J]. The Journal of experimental medicine, 2015, 212(3): 333-349.