Expression of Snail protein in tumor-stroma interface

被引:183
作者
Franci, C.
Takkunen, M.
Dave, N.
Alameda, F.
Gomez, S.
Rodriguez, R.
Escriva, M.
Montserrat-Sentis, B.
Baro, T.
Garrido, M.
Bonilla, F.
Virtanen, I.
Garcia de Herreros, A.
机构
[1] Univ Helsinki, Inst Biomed Anat, Biomedicum, FIN-00014 Helsinki, Finland
[2] Univ Pompea Fabra, Inst Municipal Invest Med, Unitat Biol Cellular & Mol, Barcelona, Spain
[3] Hosp Mar, Serv Anat Patol, E-08003 Barcelona, Spain
[4] Univ Autonoma Barcelona, Fac Med, E-08193 Barcelona, Spain
[5] Univ Pompau Fabra, Inst Municipal Invest Med, Serv Estab, Barcelona, Spain
[6] Hosp Virgen Salud, Dept Patol, Toledo, Spain
[7] Hosp Univ Puerta Hierro, Med Oncol Serv, Madrid, Spain
关键词
Snail transcriptional factor; fibroblast; epithelial-mesenchymal transition;
D O I
10.1038/sj.onc.1209519
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The product of Snail gene is a repressor of E-cadherin transcription and an inductor of the epithelial-to-mesenchymal transition in several epithelial tumor cell lines. In order to examine Snail expression in animal and human tissues, we have raised a monoclonal antibody(MAb) that reacts with the regulatory domain of this protein. Analysis of murine embryos shows that Snail is expressed in extraembryonic tissues and embryonic mesoderm, in mesenchymal cells of lungs and dermis as well as in cartilage. Little reactivity was detected in adult tissues as Snail was not constitutively expressed in most mesenchymal cells. However, Snail expression was observed in activated fibroblasts involved in wound healing in mice skin. Moreover, Snail was detected in pathological conditions causing hyperstimulation of fibroblasts, such as fibromatosis. Analysis of Snail expression in tumors revealed that it was highly expressed in sarcomas and. brosarcomas. In epithelial tumors, it presented a more limited distribution, restricted to stromal cells placed in the vicinity of the tumor and to tumoral cells in the same areas. These results demonstrate that Snail is present in activated mesenchymal cells, indicate its relevance in the communication between tumor and stroma and suggest that it can promote the conversion of carcinoma cells to stromal cells.
引用
收藏
页码:5134 / 5144
页数:11
相关论文
共 43 条
[1]   Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells [J].
Barberà, MJ ;
Puig, I ;
Domínguez, D ;
Julien-Grille, S ;
Guaita-Esteruelas, S ;
Peiró, S ;
Baulida, J ;
Francí, C ;
Dedhar, S ;
Larue, L ;
de Herreros, AG .
ONCOGENE, 2004, 23 (44) :7345-7354
[2]   The Snail genes as inducers of cell movement and survival: implications in development and cancer [J].
Barrallo-Gimeno, A ;
Nieto, MA .
DEVELOPMENT, 2005, 132 (14) :3151-3161
[3]   The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells [J].
Batlle, E ;
Sancho, E ;
Franci, C ;
Domínguez, D ;
Monfar, M ;
Baulida, J ;
de Herreros, AG .
NATURE CELL BIOLOGY, 2000, 2 (02) :84-89
[4]   Correlation of Snail expression with histological grade and lymph node status in breast carcinomas [J].
Blanco, MJ ;
Moreno-Bueno, G ;
Sarrio, D ;
Locascio, A ;
Cano, A ;
Palacios, J ;
Nieto, MA .
ONCOGENE, 2002, 21 (20) :3241-3246
[5]   The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression [J].
Cano, A ;
Pérez-Moreno, MA ;
Rodrigo, I ;
Locascio, A ;
Blanco, MJ ;
del Barrio, MG ;
Portillo, F ;
Nieto, MA .
NATURE CELL BIOLOGY, 2000, 2 (02) :76-83
[6]   The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition [J].
Carver, EA ;
Jiang, RL ;
Lan, Y ;
Oram, KF ;
Gridley, T .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (23) :8184-8188
[7]   The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion [J].
Comijn, J ;
Berx, G ;
Vermassen, P ;
Verschueren, K ;
van Grunsven, L ;
Bruyneel, E ;
Mareel, M ;
Huylebroeck, D ;
van Roy, F .
MOLECULAR CELL, 2001, 7 (06) :1267-1278
[8]   Unraveling signalling cascades for the Snail family of transcription factors [J].
De Craene, B ;
van Roy, F ;
Berx, G .
CELLULAR SIGNALLING, 2005, 17 (05) :535-547
[9]   Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor [J].
Domínguez, D ;
Montserrat-Sentís, B ;
Virgós-Soler, A ;
Guaita, S ;
Grueso, J ;
Porta, M ;
Puig, I ;
Baulida, J ;
Francí, C ;
de Herreros, AG .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) :5078-5089
[10]   Snail, slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma [J].
Elloul, S ;
Elstrand, MB ;
Nesland, JM ;
Tropé, CG ;
Kvalheim, G ;
Goldberg, I ;
Reich, R ;
Davidson, B .
CANCER, 2005, 103 (08) :1631-1643