title: Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer.
abstract: Pancreatic cancer is an aggressive malignancy with a high metastatic potential that results in a high mortality rate worldwide. Although macrophages have the potential to kill tumor cells and elicit immune responses against tumors, there is evidence that tumor-associated macrophages (TAMs) promote tumor progression and suppress T-cell responses. CC-chemokine ligand 20 (CCL20) and its unique receptor CC-chemokine receptor 6 (CCR6) are exploited by cancer cells for migration and metastasis and play important roles in the development and progression of cancer. Recent studies have shown that the expression of CCL20 is upregulated in pancreatic cancer; however, the mechanism of action of CCL20 remains to be fully elucidated. In this study, the aberrant expression of CCL20 in TAMs of pancreatic cancer tissue, including metastatic pancreatic cancer tissue, was detected. CCL20 expression was considerably higher in macrophages than in pancreatic cancer cell lines, particularly in interleukin-4-treated (M2) macrophages. Using Boyden chamber assays of pancreatic cancer cells, we found that CCL20 secreted by M2 macrophages promoted the migration, epithelial-mesenchymal transition, and invasion of pancreatic cancer cells. RNA interference results showed that CCR6 is a receptor for CCL20 in pancreatic cancer cells, mediating the increased invasive properties of these cells promoted by CCL20. Using a mouse model, we confirmed the roles of CCR6/CCL20 in promoting pancreatic cancer growth and liver metastasis in vivo Our findings provide insight into the important role of macrophage-secreted CCL20 in pancreatic cancer and implicate CCR6/CCL20 as potential therapeutic targets.
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Bingyan
authors: B
authors: Liu
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Yiping
authors: Y
authors: Jia
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Jun
authors: J
authors: Ma
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Shaoqiu
authors: S
authors: Wu
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Haosheng
authors: H
authors: Jiang
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Yan
authors: Y
authors: Cao
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Xianjun
authors: X
authors: Sun
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Xiang
authors: X
authors: Yin
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
authors: Shuo
authors: S
authors: Yan
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China myshang1969@aliyun.com maoaw_2015@163.com.
authors: Mingyi
authors: M
authors: Shang
authors: Department of Interventional Radiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China myshang1969@aliyun.com maoaw_2015@163.com.
authors: Aiwu
authors: A
authors: Mao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D054418:Chemokine CCL20 / Q000378:metabolism / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D064593:Heterografts; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D054418:Chemokine CCL20
keywords: CCL20; CCR6; pancreatic cancer metastasis; tumor-associated macrophage