Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis.
Suguru KadomotoKouji IzumiKaoru HiratsukaTaito NakanoRenato NaitoTomoyuki MakinoHiroaki IwamotoHiroshi YaegashiKazuyoshi ShigeharaYoshifumi KadonoHiroki NakataYohei SaitoKyoko Nakagawa GotoAtsushi MizokamiPublished in: Cancers (2019)
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.
Keyphrases
- induced apoptosis
- renal cell carcinoma
- epithelial mesenchymal transition
- signaling pathway
- cell cycle arrest
- endothelial cells
- cell migration
- endoplasmic reticulum stress
- adipose tissue
- stem cells
- cell death
- gene expression
- cell proliferation
- regulatory t cells
- oxidative stress
- pi k akt
- transforming growth factor
- high resolution
- high throughput
- single cell
- peripheral blood