2024-03-28T14:00:02Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/972792020-11-12T13:25:49Zcom_10261_22com_10261_1com_10261_86col_10261_275col_10261_339
Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells
Herrera, Mercedes
Alba-Castellón, Lorena
Silva, Javier
García, Vanesa
García, José M.
Gil, Beatriz
Larriba, María Jesús
Casal, J. Ignacio
García de Herreros, Antonio
Bonilla, Félix
Peña, Cristina
Comunidad de Madrid
Instituto de Salud Carlos III
Fundación Científica Asociación Española Contra el Cáncer
Banco Santander
Snail1
Cancer-associated fibroblasts
Colon cancer
Cell migration
et al.
Snail1 is a transcriptional factor that plays an important role in epithelial–mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as α-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as α-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells.
2014-05-27T08:41:20Z
2014-05-27T08:41:20Z
2014-06
artículo
International Journal of Cancer 134(12): 2984-2990 (2014)
0020-7136
http://hdl.handle.net/10261/97279
10.1002/ijc.28613
1097-0215
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100002704
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/100010784
24242829
eng
Preprint
http://dx.doi.org/10.1002/ijc.28613
Sí
S2010/BMD-2344/COLOMICS2
openAccess
John Wiley & Sons