Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22–CCR4 axis
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Aerken Maolake1, Kouji Izumi1, Kazuyoshi Shigehara1, Ariunbold Natsagdorj1, Hiroaki Iwamoto1, Suguru Kadomoto1, Yuta Takezawa1, Kazuaki Machioka1, Kazutaka Narimoto1, Mikio Namiki1, Wen-Jye Lin2, Guzailinuer Wufuer3, Atsushi Mizokami1
1Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
2Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
3Hematology Department of The People’s Hospital of Xinjiang Uyghur Autonomous Region, Xinjiang, China
Kouji Izumi, email: firstname.lastname@example.org
Keywords: tumor-associated macrophages, CCL2, prostate cancer, CCL22, CCR4
Received: September 01, 2016 Accepted: November 22, 2016 Published: December 26, 2016
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2–CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues. In vitro co-culture of prostate cancer cells and macrophages resulted in increased CCL2 and CCR2 levels in prostate cancer cells. The addition of CCL2 induced CCL22 and CCR4 production in prostate cancer cells. The migration and invasion of prostate cancer cells via enhanced phosphorylation of Akt were promoted by CCL17 and CCL22. CCR4 may be a potential candidate for molecular-targeted therapy.
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