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The role of myofibroblasts in upregulation of S100A8 and S100A9 and the differentiation of myeloid cells in the colorectal cancer microenvironment.

Authors
 Jae Hak Kim  ;  Sun-Hee OH  ;  Eo-Jin Kim  ;  Soo Jung Park  ;  Sung Pil Hong  ;  Jae Hee Cheon  ;  Tae Il Kim  ;  Won Ho Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.423(1) : 60-66, 2012 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2012
MeSH
Calgranulin A/biosynthesis* ; Calgranulin B/biosynthesis* ; Cell Differentiation ; Cell Line, Tumor ; Cell Movement ; Coculture Techniques ; Colorectal Neoplasms/pathology* ; Culture Media, Conditioned/pharmacology ; Humans ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Myeloid Cells/pathology* ; Myofibroblasts/metabolism* ; Neoplasm Invasiveness ; Tumor Microenvironment* ; Up-Regulation
Keywords
S100A8 ; S100A9 ; Myofibroblasts ; Myeloid cells ; Tumor microenvironment
Abstract
BACKGROUND/AIM: S100A8/A9 and myeloid cells in the tumor microenvironment play an important role in cancer invasion and progression, and the effect of tumor-infiltrated myofibroblasts on myeloid cells in the tumor microenvironment is relatively unknown. Accordingly, we investigated the role of myofibroblasts in the upregulation of S100A8/A9 as well as in the differentiation of myeloid cells in the colorectal cancer (CRC) microenvironment. MATERIALS AND METHODS: To investigate the interactions among cancer cells, myofibroblasts, and inflammatory cells in the microenvironment of CRC, we used 10 CRC cell lines, 18CO cells and THP-1 cells, which were co-cultured with each other or cultured in conditioned media (CM) of other cells. Expression of S100A8/A9 was evaluated via Western blot, immunohistochemical staining and immunofluorescence. The secreted factors from the cell lines were analyzed using cytokine antibody array. Flow cytometry analysis was performed to analyze the differentiation markers of myeloid cells. RESULTS: 18CO CM induced increased expression of S100A8/A9 in THP-1 cells. Increased expression of S100A8/A9 was noted in inflammatory cells of the peri- and intra-tumoral areas, along with myofibroblasts in colon cancer tissue. S100A8/A9-expressing inflammatory cells also exhibited CD68 expression in colon cancer tissue, and 18CO CM induced differentiation of THP-1 cells into myeloid-derived suppressor cells (MDSCs) or M2 macrophages expressing S100A8/A9. Significant amounts of IL-6 and IL-8 were detected in 18CO CM, compared to those in both controls and THP-1 CM, and tumor-infiltrated myofibroblasts expressed IL-8 in colon cancer tissue. Finally, neutralizing antibodies to IL-6 and IL-8 attenuated 18CO CM-induced increased expression of S100A8/A9. CONCLUSIONS: The upregulation of S100A8/A9 in tumor-infiltrated myeloid cells could be triggered by IL-6 and IL-8 released from myofibroblasts, and myofibroblasts might induce the differentiation of myeloid cells into S100A8/9-expressing MDSCs or M2 macrophages in the CRC microenvironment.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X12009588
DOI
22634002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Jae Hak(김재학)
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Park, Soo Jung(박수정)
Oh, Sun Hee(오선희)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
Hong, Sung Pil(홍성필)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89696
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