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Soluble factors derived from tumor mammary cell lines induce a stromal mammary adipose reversion in human and mice adipose cells. Possible role of TGF-β1 and TNF-α

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Abstract

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/EBPα and PPARγ. We also demonstrated that exogenous TGF-β1 and TNF-α 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/EBPα and PPARγ was tested in 3T3-L1 cells by interfering with the inhibitory effects of media with agents that block the TGF-β1 and TNF-α activity. These results allow us to postulate that TGF-β1 and TNF-α present in this media are in part responsible for this phenotypic reversion.

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Acknowledgments

This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnología (FONDECYT) of Chile.

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Authors and Affiliations

  1. Laboratory of Cellular Biology, INTA, University of Chile, Casilla 138, Santiago 11, Chile

    Javier Guerrero, Nicolás Tobar, Mónica Cáceres & Jorge Martínez

  2. East Metropolitan Health Service, Dr. Luis Tisné, Santiago, Chile

    Lorena Espinoza & Paula Escobar

  3. Digna Biotech, Madrid, Spain

    Javier Dotor

  4. Laboratory of Periodontal Physiology, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile

    Patricio C. Smith

Authors
  1. Javier Guerrero
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  2. Nicolás Tobar
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Correspondence to Jorge Martínez.

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Guerrero, J., Tobar, N., Cáceres, M. et al. Soluble factors derived from tumor mammary cell lines induce a stromal mammary adipose reversion in human and mice adipose cells. Possible role of TGF-β1 and TNF-α. Breast Cancer Res Treat 119, 497–508 (2010). https://doi.org/10.1007/s10549-009-0491-1

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  • DOI: https://doi.org/10.1007/s10549-009-0491-1

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