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Published on: October 20, 2016
M-CSFR expression in the embryonal component of hepatoblastoma and cell-to-cell interaction between macrophages and
Lianbo Li1,2,3, Tomoaki Irie1,2, Daiki Yoshii1
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuouku, Kumamoto, 860-8556, Japan.
Abstract:
Tumor-associated macrophages (TAMs) have protumor functions in various cancers. However, their significance in hepatoblastoma, the most common liver tumor in children, remains unclear. The aim of this study was to explore the potential roles of TAMs in hepatoblastoma. Immunohistochemical analysis revealed that the density of CD204-positive TAMs was significantly higher in the embryonal component than in other histological subtypes of hepatoblastoma. An in vitro co-culture study with Huh6 cells and human monocyte-derived macrophages (HMDMs) showed that macrophage-colony-stimulating factor receptor (M-CSFR) was strongly up-regulated in the Huh6 cells that were directly co-cultured with HMDMs. The expressions of M-CSFR ligands (interleukin-34 and M-CSF) were also increased by co-culture with HMDMs. The proliferation of HepG2 cells (another hepatoblastoma cell line expressing M-CSFR) was inhibited by an M-CSFR inhibitor. M-CSFR was found to be highly expressed in the embryonal component and in recurrent lesions. The number of CD204-positive macrophages was also higher in the M-CSFR-positive areas than in the M-CSFR-negative areas. Thus, M-CSFR expression appeared to be induced by cell-cell contact with macrophages in hepatoblastoma cells, and M-CSFR inhibitor is potentially effective against M-CSFR-positive hepatoblastoma, especially recurrent cases.
Insights
Tumor-associated macrophages (TAMs) promote hepatoblastoma growth. Targeting macrophage-colony-stimulating factor receptor (M-CSFR) may be effective against M-CSFR-positive hepatoblastoma, particularly in recurrent cases.
Area of Science:
- Pediatric oncology
- Cancer immunology
- Liver cancer research
Background:
- Tumor-associated macrophages (TAMs) exhibit protumor functions in many cancers.
- The role of TAMs in hepatoblastoma, a common pediatric liver tumor, is not well understood.
Purpose of the Study:
- To investigate the potential roles of TAMs in hepatoblastoma.
- To explore macrophage-colony-stimulating factor receptor (M-CSFR) as a therapeutic target in hepatoblastoma.
Main Methods:
- Immunohistochemical analysis of CD204-positive TAMs in hepatoblastoma subtypes.
- In vitro co-culture studies of hepatoblastoma cell lines (Huh6, HepG2) with human monocyte-derived macrophages (HMDMs).
- Assessment of M-CSFR and its ligand expression, and the effect of an M-CSFR inhibitor.
Main Results:
- Higher density of CD204-positive TAMs observed in the embryonal component of hepatoblastoma.
- Macrophage co-culture upregulated M-CSFR and its ligands (interleukin-34, M-CSF) in hepatoblastoma cells.
- M-CSFR inhibition suppressed proliferation in M-CSFR-expressing hepatoblastoma cells (HepG2).
- M-CSFR was highly expressed in embryonal components and recurrent lesions, correlating with higher TAM density.
Conclusions:
- M-CSFR expression in hepatoblastoma cells is induced by cell-cell contact with macrophages.
- M-CSFR inhibition shows potential efficacy against M-CSFR-positive hepatoblastoma, especially recurrent forms.
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