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Cancer Cell. 2014 May 12;25(5):605-20. doi: 10.1016/j.ccr.2014.03.021.

A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis.

Author information

  • 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Medical Oncology, No. 2 Affiliated Hospital, Guangzhou Medical College, Guangzhou 510260, China.
  • 3Department of Internal Medicine, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.
  • 4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • 5Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
  • 6Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
  • 7Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. Electronic address: songew@mail.sysu.edu.cn.

Abstract

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 GM-CSF. 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.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24823638
[PubMed - indexed for MEDLINE]
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