M-CSFR expression in the embryonal component of hepatoblastoma and cell-to-cell interaction between macrophages and hepatoblastoma
M-CSFR expression in the embryonal component of hepatoblastoma and cell-to-cell interaction between macrophages and hepatoblastoma
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DOI：
10.1007/s00795-022-00323-y
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发表时间：
2022-05
影响因子：
1.8
通讯作者：
Lian-qian Li;T. Irie;D. Yoshii;Y. Komohara;Yukio Fujiwara;Shigeyuki Esumi;M. Kadohisa;M. Honda;S. Suzu;T. Matsuura;Kenichi Kohashi;Y. Oda;T. Hibi
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文献类型：
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作者：
Lian-qian Li;T. Irie;D. Yoshii;Y. Komohara;Yukio Fujiwara;Shigeyuki Esumi;M. Kadohisa;M. Honda;S. Suzu;T. Matsuura;Kenichi Kohashi;Y. Oda;T. Hibi
肿瘤相关巨噬细胞（TAM）在多种癌症中具有促肿瘤功能。然而，它们在儿童最常见的肝脏肿瘤肝母细胞瘤中的意义尚不清楚。本研究的目的是探讨TAMs在肝母细胞瘤中的潜在作用。免疫组织化学分析显示，胚胎成分中CD 204阳性TAMs的密度显着高于肝母细胞瘤的其他组织学亚型。Huh 6细胞和人单核细胞衍生的巨噬细胞（HMDM）的体外共培养研究表明，巨噬细胞集落刺激因子受体（M-CSFR）在与HMDM直接共培养的Huh 6细胞中强烈上调。M-CSFR配体（白细胞介素-34和M-CSF）的表达也通过与HMDM共培养而增加。HepG 2细胞（另一种表达M-CSFR的肝母细胞瘤细胞系）的增殖被M-CSFR抑制剂抑制。发现M-CSFR在胚胎成分和复发性病变中高度表达。CD 204阳性巨噬细胞的数量在M-CSFR阳性区域也高于M-CSFR阴性区域。因此，M-CSFR表达似乎是通过与肝母细胞瘤细胞中的巨噬细胞的细胞-细胞接触来诱导的，并且M-CSFR抑制剂对M-CSFR阳性肝母细胞瘤，特别是复发病例可能有效。
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.