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

Authors
 Eun Kyoung Kim  ;  Sook Moon  ;  Do Kyeong Kim  ;  Xianglan Zhang  ;  Jin Kim 
Citation
 PLoS One, Vol.13(1) : e0188847, 2018 
Journal Title
 PLoS One 
Issue Date
2018
MeSH
Western Blotting ; Squamous Cell/metabolism/*pathology Carcinoma ; Cellular Senescence/*physiology ; Chemokine CXCL1/*physiology ; Coculture Techniques ; Cytokines/metabolism ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts/pathology ; Humans ; Mouth Neoplasms/metabolism/*pathology ; Neoplasm Invasiveness ; Reactive Oxygen Species/metabolism ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction
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.
Files in This Item:
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DOI
10.1371/journal.pone.0188847
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
Yonsei Authors
Kim, Do Kyeong(김도경)
Kim, Jin(김진)
Zhang, Xiang Lan(장향란)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161905
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