The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice

Naoto Yoshimura1, Ryusho Kariya2,3, Masaki Shimada1

  • 1Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Scientific Reports
|December 7, 2023
PubMed

Insights

Interleukin-17 (IL-17) promotes osteosarcoma progression and mortality by inhibiting osteoblast differentiation. Targeting IL-17 may offer a new therapeutic strategy for this common bone cancer.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Osteosarcoma is the most common primary bone tumor, with a 5-year survival rate of 70% despite advances in chemotherapy.
  • New therapeutic strategies are needed to improve outcomes for osteosarcoma patients.

Purpose of the Study:

  • To investigate the role of interleukin-17 (IL-17) in osteosarcoma progression and mortality.
  • To explore IL-17 as a potential therapeutic target for osteosarcoma.

Main Methods:

  • Utilized a mouse model of osteosarcoma with AX osteosarcoma cells.
  • Compared survival rates in wild-type, IL-17-deficient, and IL-17 receptor-deficient (IL-17RA) mice.
  • Analyzed IL-17 and IL-17RA expression in tumor tissues and patient biopsy specimens.
  • Assessed the effect of IL-17 on osteosarcoma cell differentiation.

Main Results:

  • IL-17 significantly increased osteosarcoma mortality in mice, leading to ectopic ossification and metastasis.
  • IL-17-deficient mice showed significantly prolonged survival compared to controls.
  • IL-17 inhibited osteoblast differentiation of osteosarcoma cells, maintaining their undifferentiated state.
  • IL-17RA-deficient mice exhibited survival rates comparable to wild-type mice.
  • Patient osteosarcoma samples showed higher IL-17RA expression than IL-17.

Conclusions:

  • IL-17 plays a critical role in maintaining osteosarcoma cells in an undifferentiated, malignant state.
  • IL-17 signaling is essential for osteosarcoma progression and mortality.
  • Targeting the IL-17 pathway presents a promising therapeutic avenue for osteosarcoma treatment.

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