Soluble factors derived from tumor mammary cell lines induce a stromal mammary adipose reversion in human and mice adipose cells. Possible role of TGF-beta1 and TNF-alpha.
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/EBP alpha and PPAR gamma. We also demonstrated that exogenous TGF-beta 1 and TNF-alpha 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/EBP alpha and PPAR gamma was tested in 3T3-L1 cells by interfering with the inhibitory effects of media with agents that block the TGF-beta 1 and TNF-alpha activity. These results allow us to postulate that TGF-beta 1 and TNF-alpha present in this media are in part responsible for this phenotypic reversion.
Guerrero
Javier
J
Tobar
Nicolás
N
Cáceres
Mónica
M
Espinoza
Lorena
L
Escobar
Paula
P
Dotor
Javier
J
Smith
Patricio C
PC
Martínez
Jorge
J
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D048429:Cell Size; D054338:Cell Transdifferentiation; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C530718:CEBPA protein, mouse; D017077:Culture Media, Conditioned; D047495:PPAR gamma; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha