Intratumor Heterogeneity of MIF Expression Correlates With Extramedullary Involvement of Multiple Myeloma.
Intratumor Heterogeneity of MIF Expression Correlates With Extramedullary Involvement of Multiple Myeloma.
复制标题
MIF 表达的肿瘤内异质性与多发性骨髓瘤的髓外受累相关
DOI：
10.3389/fonc.2021.694331
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Xu J;Yu N;Zhao P;Wang F;Huang J;Cui Y;Ding H;Yang Y;Gao Y;Pan L;Chang H;Wu Y;Xiang B;Gong Y;Shuai X;Hou L;Xie L;Niu T;Liu T;Zhang L;Liu W;Zhang W;Qu Y;Lin W;Zhu Y;Zhao S;Zheng Y
巨噬细胞移动抑制因子（MIF）已被证明可以促进许多恶性肿瘤的疾病进展，包括多发性骨髓瘤（MM）。我们先前报道了MIF调节MM骨髓归巢，并且MIF的敲低有利于小鼠髓外骨髓瘤的形成。在此，基于17例患者成对髓内和髓外活检骨髓瘤细胞的MIF免疫染色，我们发现髓外MM（EMM）与髓内MM（IMM）相比MIF强度较低。异种移植模型中的流式细胞术和组织学分析显示，一部分接种的人MM细胞在体内失去了它们的MIF表达（MIFLow）。值得注意的是，IMM主要具有MIFHigh细胞，而EMM显示出MIFLow细胞的比例显著增加。此外，我们从小鼠中收获髓外人MM细胞并生成单细胞转录组学数据。指出了MM细胞从MIFHigh到MIFLow状态的发育轨迹。MIFHigh细胞具有更高的增殖。MIFLow细胞更加静止，并含有丰富的核糖体蛋白基因。我们的研究结果确定了MM中MIF表达的体内差异调节，并表明MIF在疾病的髓外扩散中具有潜在的致病作用。
Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIFLow) in vivo. Of note, IMM had dominantly MIFHigh cells, while EMM showed a significantly increased ratio of MIFLow cells. Furthermore, we harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIFHigh to MIFLow state were indicated. The MIFHigh cells featured higher proliferation. The MIFLow ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified in vivo differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.
登录
查看更多内容
影响因子：
5.6
作者：
Liu, Ying;Jelloul, Fatima;Xiao, Wenbin
通讯作者：
Xiao, Wenbin
ZFPM2-AS1是一种新型lncRNA，通过稳定MIF减弱p53通路并促进胃癌发生
影响因子：
8
作者：
Kong F;Deng X;Kong X;Du Y;Li L;Zhu H;Wang Y;Xie D;Guha S;Li Z;Guan M;Xie K
通讯作者：
Xie K
影响因子：
6.5
作者：
Hedvat, CV;Comenzo, RL;Nimer, SD
通讯作者：
Nimer, SD
影响因子：
2.6
作者：
BARKER, HF;BALL, J;FRANKLIN, IM
通讯作者：
FRANKLIN, IM
影响因子：
56.9
作者：
BLOOM, BR;BENNETT, B
通讯作者：
BENNETT, B