Soluble factors derived from tumor mammary cell lines induce a stromal mammary adipose reversion in human and mice adipose cells. Possible role of TGF-b1 and TNF-a
2010
Guerrero, Javier | Tobar, Nicolás | Cáceres, Mónica | Espinoza, Lorena | Escobar, Paula | Dotor, Javier | Smith, Patricio C. | Martínez, Jorge
In carcinomas such as those of breast, pancreas, stomach, and colon, cancer cells support the expansion of molecular and cellular stroma in a phenomenon termed desmoplasia, which is characterized by a strong fibrotic response. In the case of breast tissue, in which stroma is mainly a fatty tissue, this response presumably occurs at the expense of the adipose cells, the most abundant stromal phenotype, generating a tumoral fibrous structure rich in fibroblast-like cells. In this study, we aimed to determine the cellular mechanisms by which factors present in the media conditioned by MDA-MB-231 and MCF-7 human breast cancer cell lines induce a reversion of adipose cells to a fibroblastic phenotype. We demonstrated that soluble factors generated by these cell lines stimulated the reversion of mammary adipose phenotype evaluated as intracellular lipid content and expression of C/EBPa and PPARc. We also demonstrated that exogenous TGF-b1 and TNF-a exerts a similar function. The participation of both growth factors, components of media conditioned by tumoral mammary cells, on the expression and nuclear translocation of C/EBPa and PPARc was tested in 3T3-L1 cells by interfering with the inhibitory effects of media with agents that block the TGF-b1 and TNF-a activity. These results allow us to postulate that TGF-b1 and TNF-a present in this media are in part responsible for this phenotypic reversion.
Show more [+] Less [-]This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile.
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