Abstract
We focused on Tumor-Associated Macrophages (TAM) and explored its effects on bladder cancer (BC). Co-culturing PMA-treated THP-1 with BC cell lines (UMUC3 and T24) induced THP-1 to develop suppressed CD68 and increased CD206 expression which differentiated into M2-like macrophages. Co-culture of BC with TAM of this M2-like macrophage enhanced the migration and invasive activities of BC, as well as the expression of EMT marker. Human cytokine antibody array of conditioned medium from the co-culture of BC and TAM showed high CCL20, CCL2 and CXCL7. qPCR revealed that these chemokines were mainly derived from TAMs, not BC. Only CCL20 enhanced the migration and invasion of BC and the expression of EMT markers when each of these three recombinant chemokines was administered to BC. Furthermore, inhibiting CCR6, a receptor specific for CCL20, suppressed migration and invasion as expected. In BC, TAMs promote progression and metastasis by secreting CCL20, and inhibition of CCR6 may be one potential therapeutic approach to suppress BC activity.
Citation Format: Ryunosuke Nakagawa, Izumi Kouji, Ren Toriumi, Shuhei Aoyama, Taiki Kamjima, Hiroshi Kano, Tomoyuki Makino, Renato Naito, Hiroshi Yaegashi, Takahiro Nohara, Hiroki Nakata, Atsushi Mizokami. Tumor-associated macrophages promote bladder cancer cell migration and invasion through activation of CCL20-CCR6 axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6809.