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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.
Background:
Inflammation is known to promote tumor formation and progression; however, we found a natural anti-inflammatory factor, interleukin (IL)-1 receptor antagonist (IL1RN), in a mouse transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1-derived tumor microenvironment (TME). We sought to characterize the functions of the IL1RN-secreting cells in the TME.
Methods:
We compared tumors collected from two syngeneic mouse models and isolated tumor-infiltrating leukocytes (TILs) with different cluster of differentiation 11b (CD11b) statuses. We examined the proliferation functions of the TILs and the IL1RN using several approaches, including a colony-formation assay and DNA synthesis levels.
Results:
We demonstrated that CD11b-deficient TILs (TILs/CD11b-) secreted the IL1RN and promoted proliferation by analyzing conditioned media. In addition to mouse TRAMP-C1, proliferation functions of the IL1RN were confirmed in several human castration-resistant prostate cancer (CRPC) cell lines and one normal epithelial cell line. The androgen-sensitive lymph node carcinoma of the prostate (LNCaP) cell line showed cytotoxic responses to IL1β treatment and androgen-dependent regulation of IL-1 receptor type 1 (IL1R1), while the C4-2 CRPC cell line did not. IL1RN rescued LNCaP cells from the cytotoxic effects of IL1β/IL1R1 signaling.
Conclusions:
Our results support TILs/CD11b- cells being able to protect androgen-dependent cells from inflammatory damage and promote the malignant progression of prostate cancers partly through the IL1RN in the TME.
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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07:25A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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