CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma

Eun Kyoung Kim; Sook Moon; Do Kyeong Kim; Xianglan Zhang; Jin Kim

doi:10.1371/journal.pone.0188847

CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma

Eun Kyoung Kim, Sook Moon, Do Kyeong Kim, Xianglan Zhang, Jin Kim

Department of Oral Pathology

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

14 Citations (Scopus)

Abstract

Cancer-associated fibroblasts (CAFs) have emerged as one of the main factors related to cancer progression, however, the conversion mechanism of normal fibroblasts (NOFs) to CAFs has not been well elucidated. The aim of this study was to investigate the underlying mechanism of CAF transformation from NOFs in oral squamous cell carcinoma (OSCC). This study found that NOFs exposed to OSCC cells transformed to senescent cells. The cytokine antibody array showed the highest secretion levels of IL-6 and CXCL1 in NOFs co-cultured with OSCC cells. Despite that both IL-6 and CXCL1 induced the senescent phenotype of CAFs, CXCL1 secretion showed a cancer-specific response to transform NOFs into CAFs in OSCC, whereas IL-6 secretion was eventuated by common co-culture condition. Further, CXCL1 was released from NOFs co-cultured with OSCC cells, however, CXCL1 was undetectable in mono-cultured NOFs or co-cultured OSCC cells with NOFs. Taken together, this study demonstrates that CXCL1 can transform NOFs into senescent CAFs via an autocrine mechanism. These data might contribute to further understanding of CAFs and to development of a potential therapeutic approach targeting cancer cells-CAFs interactions.

Original language	English
Article number	e0188847
Journal	PloS one
Volume	13
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0188847
Publication status	Published - 2018 Jan

Bibliographical note

Funding Information:
This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF)(http://www. nrf.re.kr/) funded by the Ministry of Education, Science and Technology [2009-0094027]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2018 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0188847

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title = "CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma",

abstract = "Cancer-associated fibroblasts (CAFs) have emerged as one of the main factors related to cancer progression, however, the conversion mechanism of normal fibroblasts (NOFs) to CAFs has not been well elucidated. The aim of this study was to investigate the underlying mechanism of CAF transformation from NOFs in oral squamous cell carcinoma (OSCC). This study found that NOFs exposed to OSCC cells transformed to senescent cells. The cytokine antibody array showed the highest secretion levels of IL-6 and CXCL1 in NOFs co-cultured with OSCC cells. Despite that both IL-6 and CXCL1 induced the senescent phenotype of CAFs, CXCL1 secretion showed a cancer-specific response to transform NOFs into CAFs in OSCC, whereas IL-6 secretion was eventuated by common co-culture condition. Further, CXCL1 was released from NOFs co-cultured with OSCC cells, however, CXCL1 was undetectable in mono-cultured NOFs or co-cultured OSCC cells with NOFs. Taken together, this study demonstrates that CXCL1 can transform NOFs into senescent CAFs via an autocrine mechanism. These data might contribute to further understanding of CAFs and to development of a potential therapeutic approach targeting cancer cells-CAFs interactions.",

author = "Kim, {Eun Kyoung} and Sook Moon and Kim, {Do Kyeong} and Xianglan Zhang and Jin Kim",

note = "Funding Information: This work was supported by the Priority Research Centers Program through the National Research Foundation of Korea (NRF)(http://www. nrf.re.kr/) funded by the Ministry of Education, Science and Technology [2009-0094027]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2018 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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N2 - Cancer-associated fibroblasts (CAFs) have emerged as one of the main factors related to cancer progression, however, the conversion mechanism of normal fibroblasts (NOFs) to CAFs has not been well elucidated. The aim of this study was to investigate the underlying mechanism of CAF transformation from NOFs in oral squamous cell carcinoma (OSCC). This study found that NOFs exposed to OSCC cells transformed to senescent cells. The cytokine antibody array showed the highest secretion levels of IL-6 and CXCL1 in NOFs co-cultured with OSCC cells. Despite that both IL-6 and CXCL1 induced the senescent phenotype of CAFs, CXCL1 secretion showed a cancer-specific response to transform NOFs into CAFs in OSCC, whereas IL-6 secretion was eventuated by common co-culture condition. Further, CXCL1 was released from NOFs co-cultured with OSCC cells, however, CXCL1 was undetectable in mono-cultured NOFs or co-cultured OSCC cells with NOFs. Taken together, this study demonstrates that CXCL1 can transform NOFs into senescent CAFs via an autocrine mechanism. These data might contribute to further understanding of CAFs and to development of a potential therapeutic approach targeting cancer cells-CAFs interactions.

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CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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