Tumor-associated macrophages promote bladder cancer metastasis through the CCL20-CCR6 axis

被引：1

作者：

Nakagawa, Ryunosuke ^{[1
]}

Izumi, Kouji ^{[1
]}

Hiratsuka, Kaoru ^{[1
]}

Inaba, Takahiro ^{[1
]}

Koketsu, Yoshiki ^{[1
]}

Toriumi, Ren ^{[1
]}

Aoyama, Shuhei ^{[1
]}

Kamijima, Taiki ^{[1
]}

Kano, Hiroshi ^{[1
]}

Makino, Tomoyuki ^{[1
]}

Naito, Renato ^{[1
]}

Kadomoto, Suguru ^{[1
]}

Iwamoto, Hiroaki ^{[1
]}

Yaegashi, Hiroshi ^{[1
]}

Kawaguchi, Shohei ^{[1
]}

Nohara, Takahiro ^{[1
]}

Shigehara, Kazuyoshi ^{[1
]}

Nakata, Hiroki ^{[2
]}

Lin, Wen-Jye ^{[3
]}

Mizokami, Atsushi ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Integrat Canc Therapy & Urol, Takaramachi13-1, Kanazawa, Ishikawa 9208640, Japan

[2] Komatsu Univ, Fac Hlth Sci, Dept Clin Engn, Komatsu, Japan

[3] Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Miaoli County, Taiwan

来源：

NEOPLASIA | 2025年 / 60卷

关键词：

Bladder cancer; Tumor assosociated Macrophage; CCL20; CCR6; PROGRESSION; EXPRESSION; GROWTH; MICROENVIRONMENT; POLARIZATION; ACTIVATION; MIGRATION; PREDICTS; RELAPSE; CXCL1;

D O I：

10.1016/j.neo.2024.101103

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：11

共 29 条

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