Targeting Tumor-Expressing CCR6 Inhibits Colorectal Cancer Progression in Mice (127.44)

Abstract

Abstract Background: CCR6/CCL20 expressed by colorectal cancer (CRC) cells. Although their interactions may play an essential role in proliferation and migration of CRC, the in vivo evidence is lacking. Methods: Expression of CCR6/CCL20 was evaluated in 130 primary tumor specimens from CRC patients. Mouse models was established by the injection of CMT93 transfected with luciferase in CCR6-/- mice, or by crossing CCR6-/- mice with APCmin/+ mice. Intratumor injection of anti-CCR6 was performed in CCR6-/- mice grafted luciferase-labeled CMT93. Luciferase intensity of CMT93 was monitored using the IVIS Imaging System. Intestinal tumor development in APCmin/+ mice was studied with a dissecting microscope. Migration of CMT-93 treated with anti-CCR6 was investigated by the Real-Time Cell Analyzer. Results: In contrast to paratumor tissues, CCR6/CCL20 predominantly expressed by tumor cells in CRC patients of all tumor stages. CCR6/CCL20 was consistently identified in CMT-93. Injection of anti-CCR6, significantly inhibited the growth of CRC in CCR6-/- mice. Knock-out of CCR6 resulted in a decrease in numbers and size of intestinal adenomas in APCmin/+ mice. Anti-CCR6 treatment markedly inhibited the migration of CMT-93 in vitro. Conclusion: The CCR6/CCL20 interaction plays an essential role in proliferation and migration of colorectal cancer cells via the autocrine mechanism in mice, and selectively targeting tumor-expressing CCR6 may harbor a novel therapeutic strategy for human CRC.