Format

Send to

Choose Destination
Nat Commun. 2017 May 26;8:15584. doi: 10.1038/ncomms15584.

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

Author information

1
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
2
Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06520, USA.
3
Center for Strategic Scientific Initiatives, National Cancer Institute, Bethesda, Maryland 20850, USA.
4
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
5
Department of Oncology and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

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.

PMID:
28548090
PMCID:
PMC5458548
DOI:
10.1038/ncomms15584
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center