期刊
CANCER CELL
卷 25, 期 5, 页码 605-620出版社
CELL PRESS
DOI: 10.1016/j.ccr.2014.03.021
关键词
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资金
- Ministry of Science and Technology of China [2010CB912800, 2011CB504203]
- Natural Science Foundation of China [81272894, 81072178, 81230060, 81261140373, 81372819]
- National S&T Major Special Project on New Drug Innovation of China [2011ZX09102-010-02]
- Science Foundation of Guangdong Province [S2012030006287]
- Translational Medicine Public Platform of Guangdong Province [4202037]
- Ministry of Education of China [20120171110075]
The close vicinity of cancer cells undergoing epithelial-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) at the invasive front of tumors suggests that these two cell type may mutually interact. We show that mesenchymal-like breast cancer cells activate macrophages to a TAM-like phenotype by GMCSF. Reciprocally, CCL18 from TAMs induces cancer cell EMT, forming a positive feedback loop, in coculture systems and humanized mice. Inhibition of GM-CSF or CCL18 breaks this loop and reduces cancer metastasis. High GM-CSF expression in breast cancer samples is associated with more CCL18(+) macrophages, cancer cell EMT, enhanced metastasis, and reduced patient survival. These findings suggest that a positive feedback loop between GM-CSF and CCL18 is important in breast cancer metastasis.
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