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

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

doi:10.1038/ncomms15584

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

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

Yonsei Advanced Science Institute

Research output: Contribution to journal › Article › peer-review

100 Citations (Scopus)

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.

Original language	English
Article number	15584
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15584
Publication status	Published - 2017 May 26

Bibliographical note

Funding Information:
This work was supported by National Cancer Institute grants (1U54CA210173-01, R01CA174388 and 5U54CA193461).

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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

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.",

author = "Hasini Jayatilaka and Pranay Tyle and Chen, {Jonathan J.} and Minsuk Kwak and Julia Ju and Kim, {Hyun Ji} and Lee, {Jerry S.H.} and Wu, {Pei Hsun} and Gilkes, {Daniele M.} and Rong Fan and Denis Wirtz",

note = "Funding Information: This work was supported by National Cancer Institute grants (1U54CA210173-01, R01CA174388 and 5U54CA193461).",

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doi = "10.1038/ncomms15584",

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AU - Jayatilaka, Hasini

AU - Tyle, Pranay

AU - Chen, Jonathan J.

AU - Kwak, Minsuk

AU - Ju, Julia

AU - Kim, Hyun Ji

AU - Lee, Jerry S.H.

AU - Wu, Pei Hsun

AU - Gilkes, Daniele M.

AU - Fan, Rong

AU - Wirtz, Denis

N1 - Funding Information: This work was supported by National Cancer Institute grants (1U54CA210173-01, R01CA174388 and 5U54CA193461).

PY - 2017/5/26

Y1 - 2017/5/26

N2 - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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