Roles of Interleukin-1 Receptor Antagonist in Prostate Cancer Progression

Yu-Ching Fan1, Kuan-Der Lee2, Yuan-Chin Tsai3,4

  • 1PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110301, Taiwan.

Biomedicines
|December 16, 2020
PubMed
Abstract

Insights

CD11b-deficient leukocytes secrete interleukin-1 receptor antagonist (IL1RN), protecting prostate cancer cells from inflammation and promoting tumor growth. This natural anti-inflammatory factor plays a key role in the tumor microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Inflammation is a known driver of tumor formation and progression.
  • Interleukin-1 receptor antagonist (IL1RN), a natural anti-inflammatory factor, was identified in the tumor microenvironment (TME) of mouse prostate cancer.
  • The function of IL1RN-secreting cells within the TME requires characterization.

Purpose of the Study:

  • To characterize the function of IL1RN-secreting cells in the prostate cancer TME.
  • To investigate the role of IL1RN in prostate cancer progression and inflammation.

Main Methods:

  • Comparison of tumors from two syngeneic mouse models.
  • Isolation and analysis of tumor-infiltrating leukocytes (TILs) based on CD11b expression.
  • Assessment of TIL and IL1RN proliferation functions using colony-formation assays and DNA synthesis measurements.
  • Analysis of conditioned media from TILs.

Main Results:

  • CD11b-deficient TILs (TILs/CD11b-) were found to secrete IL1RN and promote proliferation.
  • IL1RN's proliferative effects were confirmed in human castration-resistant prostate cancer (CRPC) cell lines and a normal epithelial cell line.
  • Androgen-sensitive LNCaP cells showed sensitivity to IL1β and IL1R1, while CRPC C4-2 cells did not.
  • IL1RN protected LNCaP cells from IL1β/IL1R1-induced cytotoxicity.

Conclusions:

  • TILs/CD11b- cells protect androgen-dependent prostate cancer cells from inflammatory damage.
  • IL1RN secreted by these cells contributes to prostate cancer malignant progression within the TME.

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