Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer
| Autor: | Shuo Yan, Xianjun Sun, Bingyan Liu, Jun Ma, Shaoqiu Wu, Hao-Sheng Jiang, Yan Cao, Mingyi Shang, Aiwu Mao, Yiping Jia, Xiang Yin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Biophysics Mice Nude chemical and pharmacologic phenomena Tumor-associated macrophage Biochemistry Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Pancreatic cancer Animals Humans Medicine Epithelial–mesenchymal transition Neoplasm Metastasis Cell Proliferation Mice Inbred BALB C Chemokine CCL20 business.industry Macrophages Cancer hemic and immune systems General Medicine respiratory system medicine.disease Pancreatic Neoplasms 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Cancer cell Cancer research Heterografts CA19-9 business |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 48:1067-1074 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmw101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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