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Roles of Interleukin-1 Receptor Antagonist in Prostate Cancer Progression.


ABSTRACT:

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 IL1? 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 IL1?/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.

SUBMITTER: Fan YC 

PROVIDER: S-EPMC7763916 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Roles of Interleukin-1 Receptor Antagonist in Prostate Cancer Progression.

Fan Yu-Ching YC   Lee Kuan-Der KD   Tsai Yuan-Chin YC  

Biomedicines 20201213 12


<h4>Background</h4>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.<h4>Methods</h4>We compared tumors collected from two syngeneic mouse models and isolated tumor-infiltrating leukocytes (TILs  ...[more]

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