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Open Access Publications from the University of California

Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines.

  • Author(s): Wu, Heng-Hsiung
  • Hwang-Verslues, Wendy W
  • Lee, Wen-Hsin
  • Huang, Chun-Kai
  • Wei, Pei-Chi
  • Chen, Chia-Lin
  • Shew, Jin-Yuh
  • Lee, Eva Y-HP
  • Jeng, Yung-Ming
  • Tien, Yu-Wen
  • Ma, Che
  • Lee, Wen-Hwa
  • et al.

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.

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