Genetically transforming human mesenchymal stem cells to sarcomas: changes in cellular phenotype and multilineage differentiation potential.
Genetically transforming human mesenchymal stem cells to sarcomas: changes in cellular phenotype and multilineage differentiation potential.
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DOI：
10.1002/cncr.24519
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发表时间：
2009-10-15
期刊：
影响因子：
6.2
通讯作者：
Gorlick, Richard
中科院分区：
文献类型：
--
作者：
Li, Nan;Yang, Rui;Zhang, Wendong;Dorfman, Howard;Rao, Pulivarthi;Gorlick, Richard
肉瘤的起源细胞尚不清楚。高级别骨肉瘤经常表现出多能分化的潜力，并且与其他一些证据一起表明，人间充质干细胞（hMSC）可能是起源细胞。分别用含人端粒酶逆转录酶（hTERT）的逆转录病毒、猴病毒40大t抗原（SV40 TAg）和含致癌性H-Ras的慢病毒转染hMSCs。观察细胞表型和多系分化能力的变化，并与标准骨肉瘤细胞系进行比较。两种不同的基因型和表型肉瘤细胞系是由相同的遗传事件产生的。hMSCs在肿瘤发生过程中，基因表达谱变得更加复杂，核型变得更加混乱。转化后的hMSC运动能力增强。除MSC-TSR4丧失成骨分化能力外，hMSC及其衍生物均可诱导成骨、成脂和成软骨分化。hMSCs在肿瘤发生过程中保留了多系分化的潜力，在相同的遗传事件下可以产生不同的肉瘤细胞系，为更好地理解hMSC的概念以及进一步研究hMSCs与骨肉瘤的关系提供了良好的模型。
The cell of origin of sarcoma is still unclear. High grade osteosarcomas frequently demonstrate the potential for multipotent differentiation and along with several other lines of evidence suggest that human mesenchymal stem cells (hMSC) might be the cell of origin. The hMSCs were transformed with retrovirus containing human telomerase reverse transcriptase (hTERT), simian virus 40 large t antigen (SV40 TAg) and lentivirus containing oncogenic H-Ras serially. The changes of cellular phenotypes and multilineage differentiation capacity were observed and compared with the standard osteosarcoma cell lines. Two distinct genotypic and phenotypic sarcoma cell lines resulted from the same genetic events. The gene expression profiles became more complicated and the karyotype became more chaotic during hMSCs' tumorigenesis. The motility of transformed hMSC was promoted. hMSC and its derivatives could be induced to osteogenic, adipogenic and chondrogenic differentiation except that MSC-TSR4 lost osteogenic differentiation capacity. Multilineage differentiation potential was retained during tumorigenesis of hMSCs and distinct sarcoma cell lines could arise with the same genetic events, providing good models in better understanding the concept of hMSC and in further investigation of the relationship of hMSCs and osteosarcomas.
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影响因子：
--
作者：
ANTILLONKLUSSMANN, F;GARCIADELGADO, M;SIERRASESUMAGA, L
通讯作者：
SIERRASESUMAGA, L
影响因子：
11.2
作者：
Linardic, CM;Downie, DL;Counter, CM
通讯作者：
Counter, CM
DOI：
10.1073/pnas.0805462105
发表时间：
2008-08-19
影响因子：
11.1
作者：
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通讯作者：
Lees, Jacqueline A.
影响因子：
16.8
作者：
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通讯作者：
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DOI：
10.1007/s00432-006-0157-x
发表时间：
2007-03-01
影响因子：
3.6
作者：
Dass, Crispin R.;Ek, Eugene T. H.;Choong, Peter F. M.
通讯作者：
Choong, Peter F. M.