Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis
We investigated the mechanisms of interaction between bladder cancer (BC) cells and tumor-associated macrophages (TAMs). Coculturing BC cell lines (UMUC3 and T24) with macrophage-like cells differentiated from THP-1 into M2-like TAMs revealed a decrease in Cluster of Differentiation (CD) 68 expressi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001441 |
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| author | Ryunosuke Nakagawa Kouji Izumi Kaoru Hiratsuka Takahiro Inaba Yoshiki Koketsu Ren Toriumi Shuhei Aoyama Taiki Kamijima Hiroshi Kano Tomoyuki Makino Renato Naito Suguru Kadomoto Hiroaki Iwamoto Hiroshi Yaegashi Shohei Kawaguchi Takahiro Nohara Kazuyoshi Shigehara Hiroki Nakata Wen-Jye Lin Atsushi Mizokami |
| author_facet | Ryunosuke Nakagawa Kouji Izumi Kaoru Hiratsuka Takahiro Inaba Yoshiki Koketsu Ren Toriumi Shuhei Aoyama Taiki Kamijima Hiroshi Kano Tomoyuki Makino Renato Naito Suguru Kadomoto Hiroaki Iwamoto Hiroshi Yaegashi Shohei Kawaguchi Takahiro Nohara Kazuyoshi Shigehara Hiroki Nakata Wen-Jye Lin Atsushi Mizokami |
| author_sort | Ryunosuke Nakagawa |
| collection | DOAJ |
| description | We investigated the mechanisms of interaction between bladder cancer (BC) cells and tumor-associated macrophages (TAMs). Coculturing BC cell lines (UMUC3 and T24) with macrophage-like cells differentiated from THP-1 into M2-like TAMs revealed a decrease in Cluster of Differentiation (CD) 68 expression and an increase in CD206 expression. This differentiation enhanced BC cell migration and invasion. Additionally, M2-like TAMs significantly increased the secretion of C–C motif chemokine ligand (CCL) 20, which promotes BC cell migration and invasion via the MEK/ERK signaling pathway through its paracrine effects. Coculturing with TAMs also elevated the expression of CC chemokine receptor (CCR) 6 in BC cells, indicating increased sensitivity to CCL20. Immunohistochemistry analysis of human BC tissues showed a significant correlation between CCR6 expression levels and BC prognosis. Inhibition of CCR6 reduced BC cell metastasis both in vitro and in vivo. Additionally, CXCL1 secretion from BC cells was found to contribute to the M2-like polarization of macrophages and to enhance BC cell migration and invasion through autocrine and indirect effects. In summary, CCL20 and CXCL1 play crucial roles in the interaction between BC cells and TAMs. |
| format | Article |
| id | doaj-art-3cb609cd250f48248e5489df3c4f2da0 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-3cb609cd250f48248e5489df3c4f2da02025-02-03T04:16:32ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101103Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axisRyunosuke Nakagawa0Kouji Izumi1Kaoru Hiratsuka2Takahiro Inaba3Yoshiki Koketsu4Ren Toriumi5Shuhei Aoyama6Taiki Kamijima7Hiroshi Kano8Tomoyuki Makino9Renato Naito10Suguru Kadomoto11Hiroaki Iwamoto12Hiroshi Yaegashi13Shohei Kawaguchi14Takahiro Nohara15Kazuyoshi Shigehara16Hiroki Nakata17Wen-Jye Lin18Atsushi Mizokami19Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Correspondence author at: Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Science, Kanazawa University, Takaramachi13-1, Kanazawa, Ishikawa 920-8640, Japan.Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanDepartment of Clinical Engineering, Faculty of Health Sciences, Komatsu University, Komatsu, JapanImmunology Research Center, National Health Research Institutes, Zhunan, Miaoli County, TaiwanDepartment of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanWe investigated the mechanisms of interaction between bladder cancer (BC) cells and tumor-associated macrophages (TAMs). Coculturing BC cell lines (UMUC3 and T24) with macrophage-like cells differentiated from THP-1 into M2-like TAMs revealed a decrease in Cluster of Differentiation (CD) 68 expression and an increase in CD206 expression. This differentiation enhanced BC cell migration and invasion. Additionally, M2-like TAMs significantly increased the secretion of C–C motif chemokine ligand (CCL) 20, which promotes BC cell migration and invasion via the MEK/ERK signaling pathway through its paracrine effects. Coculturing with TAMs also elevated the expression of CC chemokine receptor (CCR) 6 in BC cells, indicating increased sensitivity to CCL20. Immunohistochemistry analysis of human BC tissues showed a significant correlation between CCR6 expression levels and BC prognosis. Inhibition of CCR6 reduced BC cell metastasis both in vitro and in vivo. Additionally, CXCL1 secretion from BC cells was found to contribute to the M2-like polarization of macrophages and to enhance BC cell migration and invasion through autocrine and indirect effects. In summary, CCL20 and CXCL1 play crucial roles in the interaction between BC cells and TAMs.http://www.sciencedirect.com/science/article/pii/S1476558624001441Bladder cancerTumor assosociated MacrophageCCL20CCR6 |
| spellingShingle | Ryunosuke Nakagawa Kouji Izumi Kaoru Hiratsuka Takahiro Inaba Yoshiki Koketsu Ren Toriumi Shuhei Aoyama Taiki Kamijima Hiroshi Kano Tomoyuki Makino Renato Naito Suguru Kadomoto Hiroaki Iwamoto Hiroshi Yaegashi Shohei Kawaguchi Takahiro Nohara Kazuyoshi Shigehara Hiroki Nakata Wen-Jye Lin Atsushi Mizokami Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis Neoplasia: An International Journal for Oncology Research Bladder cancer Tumor assosociated Macrophage CCL20 CCR6 |
| title | Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis |
| title_full | Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis |
| title_fullStr | Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis |
| title_full_unstemmed | Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis |
| title_short | Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis |
| title_sort | tumor associated macrophages promote bladder cancer metastasis through the ccl20 ccr6 axis |
| topic | Bladder cancer Tumor assosociated Macrophage CCL20 CCR6 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001441 |
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