title: Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis.
abstract: 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.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Aerken
authors.initials: A
authors.lastname: Maolake
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shigehara
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Ariunbold
authors.initials: A
authors.lastname: Natsagdorj
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Kadomoto
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Takezawa
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Machioka
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Narimoto
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.affiliation: Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Wen-Jye
authors.initials: WJ
authors.lastname: Lin
authors.affiliation: Hematology Department of The People's Hospital of Xinjiang Uyghur Autonomous Region, Xinjiang, China.
authors.forename: Guzailinuer
authors.initials: G
authors.lastname: Wufuer
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
mesh_terms: D002450:Cell Communication; D002465:Cell Movement; D054414:Chemokine CCL17 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D054398:Receptors, CCR4 / Q000378:metabolism*; D015398:Signal Transduction; D000074084:THP-1 Cells; D059016:Tumor Microenvironment; D020298:U937 Cells
chemical_list: C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515334:CCR2 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D054390:Receptors, CCR2; D054398:Receptors, CCR4; D051057:Proto-Oncogene Proteins c-akt
keywords: CCL2; CCL22; CCR4; prostate cancer; tumor-associated macrophages