Human mesenchymal stem cell transformation is associated with a mesenchymal-epithelial transition

被引:81
作者
Rubio, Daniel [2 ]
Garcia, Silvia [1 ]
De la Cueva, Teresa [3 ]
Paz, M. F. [1 ]
Lloyd, Alison C. [4 ]
Bernad, Antonio [1 ]
Garcia-Castro, Javier [5 ]
机构
[1] CNIC, Dept Regenerat Cardiol, E-28029 Madrid, Spain
[2] Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain
[3] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain
[4] UCL, London WC1E 6BT, England
[5] Ctr Invest Biomed, Andalusian Branch, Spanish Stem Cell Bank, E-18100 Granada, Spain
关键词
transformation; tumor; mesenchymal stem cell;
D O I
10.1016/j.yexcr.2007.11.017
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Carcinomas are widely thought to derive from epithelial cells with malignant progression often associated with an epithelial-mesenchymal transition (EMT). We have characterized tumors generated by spontaneously transformed human mesenchymal cells (TMC) previously obtained in our laboratory. Immunohistopathological analyses identified these tumors as poorly differentiated carcinomas, suggesting that a mesenchymal-epithelial transition (MET) was involved in the generation of TMC. This was corroborated by microarray and protein expression analysis that showed that almost all mesenchymal-related genes were severely repressed in these TMC. Interestingly, TMC also expressed embryonic antigens and were able to integrate into developing blastocysts with no signs of tumor formation, suggesting a dedifferentiation process was associated with the mesenchymal stem cell (MSC) transformation. These findings support the hypothesis that some carcinomas are derived from mesenchymal rather than from epithelial precursors. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:691 / 698
页数:8
相关论文
共 37 条
[1]  
Blelloch RH, 2004, P NATL ACAD SCI USA, V101, P13985, DOI 10.1073/pnas.0405015101
[2]   Opinion - Migrating cancer stem cells - an integrated concept of malignant tumour progression [J].
Brabletz, T ;
Jung, A ;
Spaderna, S ;
Hlubek, F ;
Kirchner, T .
NATURE REVIEWS CANCER, 2005, 5 (09) :744-749
[3]   Sheep cloned by nuclear transfer from a cultured cell line [J].
Campbell, KHS ;
McWhir, J ;
Ritchie, WA ;
Wilmut, I .
NATURE, 1996, 380 (6569) :64-66
[4]   Differentiation plasticity regulated by TGF-β family proteins in development and disease [J].
Derynck, Rik ;
Akhurst, Rosemary J. .
NATURE CELL BIOLOGY, 2007, 9 (09) :1000-1004
[5]   The molecular repertoire of the 'almighty' stem cell [J].
Eckfeldt, CE ;
Mendenhall, EM ;
Verfaillie, CM .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (09) :726-737
[6]   Stem cells: a lesson from dedifferentiation [J].
Grafi, G ;
Avivi, Y .
TRENDS IN BIOTECHNOLOGY, 2004, 22 (08) :388-389
[7]   The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it [J].
Hay, ED .
DEVELOPMENTAL DYNAMICS, 2005, 233 (03) :706-720
[8]   WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts [J].
Hosono, S ;
Luo, X ;
Hyink, DP ;
Schnapp, LM ;
Wilson, PD ;
Burrow, CR ;
Reddy, JC ;
Atweh, GF ;
Licht, JD .
ONCOGENE, 1999, 18 (02) :417-427
[9]   Gastric cancer originating from bone marrow-derived cells [J].
Houghton, J ;
Stoicov, C ;
Nomura, S ;
Rogers, AB ;
Carlson, J ;
Li, HC ;
Cai, X ;
Fox, JG ;
Goldenring, JR ;
Wang, TC .
SCIENCE, 2004, 306 (5701) :1568-1571
[10]   Epithelial-mesenchymal transitions:: Twist in development and metastasis [J].
Kang, YB ;
Massagué, J .
CELL, 2004, 118 (03) :277-279