Mature adipocytes are excellent candidates to influence
tumor behavior through heterotypic signaling processes since these cells produce
hormones,
growth factors,
cytokines and other molecules, a heterogeneous group of molecules named
adipokines. Using a 2D coculture system, we demonstrate that
breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector
kinase Chk1, a phenotype that was associated with decreased cell death as compared to
tumor cells grown alone. Interestingly, the adipocytes-induced
tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of
IL-6 expression in
tumor cells, whose activity may well account for the observed
tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this
cytokine as
tumor cells incubated after irradiation with recombinant
IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of
tumor-surrounding adipocytes in fostering a radioresistant phenotype in
breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.