ALCAM(+) stromal cells: role in giant cell tumor of bone progression.

ALCAM(+) stromal cells: role in giant cell tumor of bone progression.
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ALCAM( ) 基质细胞:在骨巨细胞瘤进展中的作用

DOI:
10.1038/s41419-018-0361-z
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发表时间:
2018-02-20
影响因子:
9
通讯作者:
Xiao J
Xiao J
中科院分区:
生物学1区
文献类型:
--
作者:
Zhou Z;Li Y;Wang X;Hu J;Kuang M;Wang Z;Li S;Xu W;Xiao J

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骨巨细胞瘤(GCTB)是一种特殊的良性肿瘤,具有不同的侵袭性和复发率。越来越多的证据表明,一个称为癌症干细胞(CSC)的细胞亚群作为癌症起始细胞存在于一系列恶性肿瘤中。然而,CSC在良性肿瘤如GCTB中的作用仍然未知,并且CSC的存在与GCTB的生物学特性之间的联系尚不清楚。为了研究这个问题,我们筛选了一组正常干细胞和CSC的标志物,发现ALCAM+基质细胞具有干细胞样细胞的特征。随后进行了一系列的实验,如细胞增殖、迁移和侵袭实验,以研究ALCAM+基质细胞的体内和体外生物学特性。采用Kaplan-Meier分析进一步评价ALCAM表达的临床意义。ALCAM+ GCTB细胞具有自我更新的干细胞特性,并具有体外分化能力。ALCAM+ GCTB细胞显示出对化疗或放射诱导的细胞死亡的抗性增加。ALCAM敲低降低GCTB细胞中的干/祖细胞特征。此外,ALCAM表达与GCTB患者的结局相关。我们的工作首次证明了基质GCTB细胞内的ALCAM+致瘤亚群,并可能代表侵袭性和复发性GCTB的潜在治疗靶点。
Giant cell tumor of bone(GCTB) is a special benign tumor with variable aggressiveness and recurrence rate. Increasing evidences suggest that a subset of cells called cancer stem cells (CSCs) are present as cancer-initiating cells in a range of malignant tumors. However, the role of CSCs in benign tumor such as GCTB remains unknown, and the connection between the presence of CSCs and biological characteristics of GCTB is unclear. To investigate this issue, we screened a panel of markers of normal stem cells and CSCs and found ALCAM+ stromal cells possessed characteristics of stem-like cells. Subsequently a series of experiments such cell proliferation, migration and invasion assays were performed to investigate the biological characteristics of ALCAM+ stromal cells in vivo and in vitro. The clinical significance of ALCAM expression were further evaluated using Kaplan-Meier analyses. The ALCAM+ GCTB cells showed the stem cell properties of self renewal and had the capacity to differentiate in vitro. The ALCAM+ GCTB cells showed increased resistance for chemotherapy- or radiation-induced cell death. ALCAM knockdown reduced stem/progenitor characteristics in GCTB Cells. Furthermore, ALCAM expression was associated with outcome in GCTB patients. Our work demonstrates for the first time ALCAM+ tumorigenic sub-population within stromal GCTB cells and may represent a potential therapeutic target in aggressive and recurrent GCTBs.
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