Hypoxia increases CX3CR1 expression via HIF-1 and NF‑κB in androgen-independent prostate cancer cells

Xiao,Li-Jie; Chen,Yuan-Yuan; Lin,Ping; Zou,Hai-Feng; Lin,Feng; Zhao,Li-Nan; Li,Dong; Guo,Liang; Tang,Jie-Bing; Zheng,Xiu-Lan; Yu,Xiao-Guang

doi:10.3892/ijo.2012.1610

Hypoxia increases CX3CR1 expression via HIF-1 and NF‑κB in androgen-independent prostate cancer cells

Authors:
- Li-Jie Xiao
- Yuan-Yuan Chen
- Ping Lin
- Hai-Feng Zou
- Feng Lin
- Li-Nan Zhao
- Dong Li
- Liang Guo
- Jie-Bing Tang
- Xiu-Lan Zheng
- Xiao-Guang Yu
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Affiliations: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin 150081, Heilongjiang, P.R. Chin, Department of Diagnosis, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, Heilongjiang, P.R. China
Published online on: August 27, 2012 https://doi.org/10.3892/ijo.2012.1610
Pages: 1827-1836

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Abstract

The unique CX3C chemokine CX3CL1 and its cognate receptor CX3CR1 have been implicated in organ-specific metastasis of various types of tumors. Hypoxia, a common phenomenon in solid tumors, is associated with a malignant cancer phenotype. Previous studies have proved that hypoxia facilitates cancer cell metastasis through upregulation of specific chemokine receptors. We hypothesized that hypoxia could upregulate CX3CR1 expression and lead to an increased chemotactic response to CX3CL1 in prostate cancer cells. In the present study, we found that CX3CR1 expression was significantly increased in androgen-independent prostate cancer cells, including DU145, PC-3 and PC-3M, following exposure to hypoxia. This upregulation of CX3CR1 corresponded to a significant increase in migration and invasion of prostate cancer cells under hypoxic conditions, which was attenuated after knocking down CX3CR1 expression. In addition, we examined the possible role of HIF-1 and NF-κB in the process of hypoxia-induced CX3CR1 expression and hypoxia-mediated metastasis. Attenuation of HIF-1 and NF-κB transcriptional activity by siRNAs or pharmacological inhibitors, abrogated hypoxia-induced upregulation of CX3CR1, and also prevented the migration and invasion of DU145 cells under a hypoxic environment. In summary, our study demonstrated that HIF-1 and NF-κB are essential for hypoxia-regulated CX3CR1 expression, which is associated with increased migratory and invasive potential of prostate cancer cells. CX3CR1 signaling is a potential therapeutic target in the adjuvant treatment of prostate cancer.

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