Inflammatory suppressive effect of prostate cancer cells with prolonged exposure to transforming growth factor β on macrophage‑differentiated cells via downregulation of prostaglandin E2

Hayashi,Akinobu; Hirokawa,Yoshifumi  S.; Kagaya,Michiko; Fujiwara,Masaya; Yoneda,Misao; Kanayama,Kazuki; Uchida,Katsunori; Ishii,Kenichiro; Shiraishi,Taizo

doi:10.3892/ol.2014.2402

Inflammatory suppressive effect of prostate cancer cells with prolonged exposure to transforming growth factor β on macrophage‑differentiated cells via downregulation of prostaglandin E2

Authors:
- Akinobu Hayashi
- Yoshifumi S. Hirokawa
- Michiko Kagaya
- Masaya Fujiwara
- Misao Yoneda
- Kazuki Kanayama
- Katsunori Uchida
- Kenichiro Ishii
- Taizo Shiraishi
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Affiliations: Department of Oncologic Pathology, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 510‑0226, Japan
Published online on: August 1, 2014 https://doi.org/10.3892/ol.2014.2402
Pages: 1513-1518

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Abstract

Transforming growth factor β1 (TGFβ1) regulates a variety of cellular functions, including cell growth, apoptosis and differentiation. The aim of the current study was to investigate the alterations of phenotypic events in the long‑term exposure of prostate cancer (PCa) cells to TGFβ1 and its effect on macrophage‑differentiated cells. The PCa cell line, PC‑3, and the subclone, M1, were exposed to TGFβ1 for short‑ or long‑term periods. TGFβ1 signaling was assessed by Smad3 phosphorylation, and non‑canonical signaling was analyzed by quantitative polymerase chain reaction‑based regulatory gene expression profiles. TGFβ1‑exposed PCa cells were also co‑cultured with phorbol 12‑myristate 13‑acetate (PMA)‑treated THP‑1 macrophages as a model of the tumor microenvironment. The phosphorylation of Smad3 in the PCa cells with long‑term exposure was lower than that in the PCa cells with short‑term exposure. Interleukin‑6 mRNA expression in the PMA‑treated THP‑1 macrophages was significantly downregulated by co‑culture with the PCa cells with long‑term exposure. Cyclooxygenase‑2 expression in the long‑term TGFβ1‑exposed PCa cells was lower than that in the control PCa cells, and the production of prostaglandin E2 (PGE2) in the long‑term TGFβ1‑exposed PCa cells was also significantly lower. The results of the current study demonstrated that the long‑term TGFβ1 exposure of PCa cells induces phenotypic changes, including the downregulation of PGE2 production. This indicates that prolonged TGFβ‑exposed PCa cells may change the cytokine production of macrophages in the tumor microenvironment.

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