Heterogeneity and immunophenotypic plasticity of malignant cells in human liposarcomas.
Heterogeneity and immunophenotypic plasticity of malignant cells in human liposarcomas.
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DOI：
10.1016/j.scr.2013.04.011
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Kolonin, Mikhail G.
中科院分区：
文献类型：
--
作者：
Zhang, Yan;Young, Eric D.;Bill, Katelynn;Belousov, Roman;Peng, Tingsheng;Lazar, Alexander J.;Pollock, Raphael E.;Simmons, Paul J.;Lev, Dina;Kolonin, Mikhail G.
脂肪肉瘤是发生于白色脂肪组织（WAT）的肿瘤，具有局部复发的倾向。侵袭性去分化脂肪肉瘤（DDLS）可能在疾病进展时由分化良好的亚型（WDLS）引起，然而，这一关键问题在很大程度上由于对脂肪肉瘤细胞组成的知识空白而未得到解决。在这里，我们希望提高对脂肪肉瘤细胞层次的认识。肿瘤切片分析表明，基于CD34（脂肪祖细胞的标志物）和CD36（脂肪细胞分化的标志物）的表达可区分的群体在WDLS和DDLS中占据不同的肿瘤内位置。利用这些标志物，我们从一组新鲜的人类手术标本中分离出荧光激活细胞分选（FACS）的细胞。基于染色体分析和组成群体的培养表型，我们表明，恶性细胞包括四个间充质群体区分的CD34和CD36的表达，而血管（CD31+）和造血（CD45+）组件是非肿瘤。最后，我们表明，小鼠异种移植物是来自CD36阴性和CD36阳性DDLS细胞，每个人口重建体内的异质性CD36表达。结合，我们的研究结果表明，恶性细胞在WDLS和DDLS可以分类根据不同阶段的脂肪形成和恶性脂肪肉瘤细胞的免疫表型可塑性。
Liposarcomas are tumors arising in white adipose tissue (WAT) with avidity for local recurrence. Aggressive dedifferentiated liposarcomas (DDLS) may arise from well-differentiated subtypes (WDLS) upon disease progression, however, this key issue is unresolved due in large part to knowledge gaps about liposarcoma cellular composition. Here, we wished to improve insights into liposarcoma cellular hierarchy. Tumor section analysis indicated that the populations, distinguishable based on expression of CD34 (a marker of adipocyte progenitors) and CD36 (a marker of adipocyte differentiation), occupy distinct intra-tumoral locations in both WDLS and DDLS. Taking advantage of these markers, we separated cells from a panel of fresh human surgical specimens by fluorescence-activated cell sorting (FACS). Based on chromosome analysis and the culture phenotypes of the composing populations, we demonstrate that malignant cells comprise four mesenchymal populations distinguished by expression of CD34 and CD36, while vascular (CD31+) and hematopoietic (CD45+) components are non-neoplastic. Finally, we show that mouse xenografts are derivable from both CD36-negative and CD36-positive DDLS cells, and that each population recreates the heterogeneity of CD36 expression in vivo. Combined, our results show that malignant cells in WDLS and DDLS can be classified according to distinct stages of adipogenesis and indicate immonophenotypic plasticity of malignant liposarcoma cells.
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影响因子：
23.9
作者：
Caplan AI;Correa D
通讯作者：
Correa D
DOI：
10.1158/1078-0432.ccr-11-1916
发表时间：
2012-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Klopp AH;Zhang Y;Solley T;Amaya-Manzanares F;Marini F;Andreeff M;Debeb B;Woodward W;Schmandt R;Broaddus R;Lu K;Kolonin MG
通讯作者：
Kolonin MG
影响因子：
64.5
作者：
Rodeheffer, Matthew S.;Birsoy, Kivanc;Friedman, Jeffrey M.
通讯作者：
Friedman, Jeffrey M.
影响因子：
2.1
作者：
Dick, JE;Lapidot, T
通讯作者：
Lapidot, T
DOI：
10.1007/bf01600148
发表时间：
1991-01-01
期刊：
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY
影响因子：
--
作者：
MECHTERSHEIMER, G
通讯作者：
MECHTERSHEIMER, G