TY - JOUR
T1 - Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells
AU - Herrera, Alberto
AU - Herrera, Mercedes
AU - Alba-Castellõn, Lorena
AU - Silva, Javier
AU - García, Vanesa
AU - Loubat-Casanovas, Jordina
AU - Álvarez-Cienfuegos, Ana
AU - Miguel García, José
AU - Rodriguez, Rufo
AU - Gil, Beatriz
AU - Jesús Citores, M.
AU - Jesús Larriba, M.
AU - Ignacio Casal, J.
AU - De Herreros, Antonio García
AU - Bonilla, Félix
AU - Peña, Cristina
PY - 2014/6/15
Y1 - 2014/6/15
N2 - 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. What's new? When colon tumors express the transcription factor Snail1, it's bad news for the patient: chances of survival are lower. But how does this protein spur cancer? In this paper, the authors examined the effects of Snail1 in fibroblasts cultured together with colon cells. By manipulating Snail1 levels in the fibroblasts, they showed that the protein controls migration and proliferation of the nearby colon cells. In mice, Snail1 was required for colon cancer cell growth and invasion.
AB - 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. What's new? When colon tumors express the transcription factor Snail1, it's bad news for the patient: chances of survival are lower. But how does this protein spur cancer? In this paper, the authors examined the effects of Snail1 in fibroblasts cultured together with colon cells. By manipulating Snail1 levels in the fibroblasts, they showed that the protein controls migration and proliferation of the nearby colon cells. In mice, Snail1 was required for colon cancer cell growth and invasion.
KW - Snail1
KW - cancer-associated fibroblasts
KW - cell migration
KW - cell proliferation
KW - colon cancer
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U2 - 10.1002/ijc.28613
DO - 10.1002/ijc.28613
M3 - Article
C2 - 24242829
AN - SCOPUS:84897990378
SN - 0020-7136
VL - 134
SP - 2984
EP - 2990
JO - International journal of cancer
JF - International journal of cancer
IS - 12
ER -