Cancer-associated adipocytes promotes breast tumor radioresistance
Cancer-associated adipocytes promotes breast tumor radioresistance
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DOI：
10.1016/j.bbrc.2011.06.101
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发表时间：
2011-07-22
影响因子：
3.1
通讯作者：
Muller, Catherine
中科院分区：
文献类型：
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作者：
Bochet, Ludivine;Meulle, Aline;Muller, Catherine
成熟脂肪细胞是通过异型信号传导过程影响肿瘤行为的极好候选者，因为这些细胞产生激素、生长因子、细胞因子和其他分子，称为脂肪因子的异质性分子组。使用2D共培养系统，我们证明了乳腺肿瘤细胞先前与成熟脂肪细胞共培养表现出辐射抗性和更早和更高的效应激酶Chk 1的增加，与单独生长的肿瘤细胞相比，与细胞死亡减少相关的表型。有趣的是，在暴露于IR之前的共培养时间期间发生的脂肪细胞诱导的肿瘤变化足以赋予抗辐射效应。在脂肪细胞引起的变化中，最引人注目的是肿瘤细胞中IL-6表达的显著增加，其活性可以很好地解释所观察到的肿瘤细胞免受IR毒性的保护。事实上，我们的数据证实了这种细胞因子的保护作用，因为在用重组IL-6照射后孵育的肿瘤细胞表现出Chk 1磷酸化增加和放射抗性表型，从而概括了在脂肪细胞存在下观察到的作用。我们目前的研究揭示了肿瘤周围脂肪细胞在乳腺肿瘤中培养放射抗性表型的新作用，这一发现可能对经常表现出侵袭性疾病的肥胖患者具有重要的临床意义。(C)2011 Elsevier Inc. All rights reserved.
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. (C) 2011 Elsevier Inc. All rights reserved.