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

Author information

Affiliations

  • 1. Guangdong 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.
      Authors
    • Su S 1
    • Liu Q 1
    • Chen J 1
    • Chen F 1
    • He C 1
    • Huang D 1
    • Wu W 1
    • Li H 1
    • Su F 1
    • Song E 1
    (10 authors)
  • 2. Guangdong 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.
      Authors
    • Chen J 2
    (1 author)
  • 3. Department of Internal Medicine, The First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.
      Authors
    • Lin L 3
    (1 author)
  • 4. Guangdong 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.
      Authors
    • Huang W 4
    • Cui X 4
    • Zheng F 4
    (3 authors)
  • 5. Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
      Authors
    • Zhang J 5
    (1 author)
    • Show all (6)

ORCIDs linked to this article

Cancer Cell, 01 May 2014, 25(5):605-620
https://doi.org/10.1016/j.ccr.2014.03.021 PMID: 24823638 

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.

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Read article at publisher's site: https://doi.org/10.1016/j.ccr.2014.03.021

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S1535610814001275/pdfUnpaywall

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