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Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration

Author

Listed:
  • Hasini Jayatilaka

    (The Johns Hopkins University)

  • Pranay Tyle

    (The Johns Hopkins University)

  • Jonathan J. Chen

    (Yale University)

  • Minsuk Kwak

    (Yale University)

  • Julia Ju

    (The Johns Hopkins University)

  • Hyun Ji Kim

    (The Johns Hopkins University)

  • Jerry S. H. Lee

    (The Johns Hopkins University
    Center for Strategic Scientific Initiatives, National Cancer Institute)

  • Pei-Hsun Wu

    (The Johns Hopkins University
    Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University)

  • Daniele M. Gilkes

    (The Johns Hopkins University
    Johns Hopkins University School of Medicine)

  • Rong Fan

    (Yale University)

  • Denis Wirtz

    (The Johns Hopkins University
    Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University
    Johns Hopkins University School of Medicine)

Abstract

Following uncontrolled proliferation, a subset of primary tumour cells acquires additional traits/mutations to trigger phenotypic changes that enhance migration and are hypothesized to be the initiators of metastasis. This study reveals an adaptive mechanism that harnesses synergistic paracrine signalling via IL-6/8, which is amplified by cell proliferation and cell density, to directly promote cell migration. This effect occurs in metastatic human sarcoma and carcinoma cells– but not in normal or non-metastatic cancer cells-, and likely involves the downstream signalling of WASF3 and Arp2/3. The transcriptional phenotype of high-density cells that emerges due to proliferation resembles that of low-density cells treated with a combination of IL-6/8. Simultaneous inhibition of IL-6/8 receptors decreases the expression of WASF3 and Arp2/3 in a mouse xenograft model and reduces metastasis. This study reveals a potential mechanism that promotes tumour cell migration and infers a strategy to decrease metastatic capacity of tumour cells.

Suggested Citation

  • Hasini Jayatilaka & Pranay Tyle & Jonathan J. Chen & Minsuk Kwak & Julia Ju & Hyun Ji Kim & Jerry S. H. Lee & Pei-Hsun Wu & Daniele M. Gilkes & Rong Fan & Denis Wirtz, 2017. "Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15584
    DOI: 10.1038/ncomms15584
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    Cited by:

    1. Reetta Peltonen & Mathias H Gramkow & Christian Dehlendorff & Pia J Osterlund & Julia S Johansen & Helena Isoniemi, 2020. "Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases," PLOS ONE, Public Library of Science, vol. 15(8), pages 1-18, August.

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