MP18-06 TUMOR-ASSOCIATED MACROPHAGES INDUCE MIGRATION OF RENAL CELL CARCINOMA CELLS VIA ACTIVATION OF THE CCL20-CCR6 AXIS

Abstract

INTRODUCTION AND OBJECTIVE: Tumor-associated macrophages (TAMs) play important roles in cancer progression, and a variety of chemokines and their receptors are involved. This study investigated macrophages and chemokine activity in the microenvironment of renal cell carcinoma (RCC). METHODS: Human monocyte cell lines THP-1 and U937 cells were stimulated with Phorbol 12-myristate 13-acetate to differentiate into macrophage-like cells. Macrophage-like cells showed M1-type characteristics as they were, and those cultured in the conditioned medium of ACHN and Caki-1 cells, which are human RCC cell line cells, showed M2-type. ACHN and Caki-1 were co-cultured with these cells, and their proliferation ability and migration ability were evaluated. We identified chemokines that were thought to have affected the results and examined their impact. RESULTS: Via a co-culture with macrophage-like cells, the migration ability of ACHN and Caki-1 cells was significantly increased, as was the epithelial–mesenchymal transition change (EMT). 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, EMT, and Akt phosphorylation in the ACHN and Caki-1 cells (Figure1). Akt inhibitor AZD5363 also decreased the EMT 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 (Figure2). CONCLUSIONS: In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by TAMs through Akt activation, followed by EMT and an acquired migration ability to metastasize. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.Source of Funding: The authors declare no conflicts of interest associated with this manuscript.