Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis

被引：41

作者：

Kadomoto, Suguru ^{[1
]}

Izumi, Kouji ^{[1
]}

Hiratsuka, Kaoru ^{[1
]}

Nakano, Taito ^{[1
]}

Naito, Renato ^{[1
]}

Makino, Tomoyuki ^{[1
]}

Iwamoto, Hiroaki ^{[1
]}

Yaegashi, Hiroshi ^{[1
]}

Shigehara, Kazuyoshi ^{[1
]}

Kadono, Yoshifumi ^{[1
]}

Nakata, Hiroki ^{[2
]}

Saito, Yohei ^{[3
]}

Nakagawa-Goto, Kyoko ^{[3
]}

Mizokami, Atsushi ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Integrat Canc Therapy & Urol, Kanazawa, Ishikawa 9208641, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Histol & Cell Biol, Kanazawa, Ishikawa 9208641, Japan

[3] Kanazawa Univ, Sch Pharmaceut Sci, Coll Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa 9201192, Japan

来源：

CANCERS | 2020年 / 12卷 / 01期

关键词：

CCL20; CCR6; migration; renal cell carcinoma; tumor-associated macrophages; CANCER CELLS; PROMOTES; PROGRESSION; METASTASIS; RECRUITMENT; CCL20/CCR6; INVASION; PATHWAY; EMT;

D O I：

10.3390/cancers12010089

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial-mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial-mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial-mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial-mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

引用

页数：13

共 27 条

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