Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential.
Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential.
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DOI：
10.1038/srep43774
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发表时间：
2017-03-06
影响因子：
4.6
通讯作者：
Stewart AG
中科院分区：
文献类型：
--
作者：
Fietz ER;Keenan CR;López-Campos G;Tu Y;Johnstone CN;Harris T;Stewart AG
糖皮质激素通常用于预防化疗引起的恶心和呕吐，尽管对其对癌症进展的直接影响缺乏了解。最近的研究表明，糖皮质激素可以抑制癌细胞的迁移。然而，这一作用尚未在雌激素受体(ER)阴性的乳腺肿瘤细胞中进行研究，尽管糖皮质激素受体(GR)的激活与ER阴性乳腺癌的预后较差有关。在本研究中，我们探讨了糖皮质激素对ER阴性的人乳腺癌细胞株MDA-MB-231和体内循环产生的高转移细胞株MDA-MB-231-HM.LNm5迁移的影响。我们首次发现糖皮质激素抑制了MDA-MB-231细胞的二维和三维迁移。选择高转移潜能的细胞导致迁移较少的细胞表型，这种表型抵抗糖皮质激素的调节，并显示GR受体表达降低。在转移选择过程中糖皮质激素耐药的出现可能部分解释了关于糖皮质激素在癌症中的作用的临床和体外证据之间的明显差异。这些发现突出了肿瘤细胞的高度可塑性，并强调了更充分地了解糖皮质激素治疗对转移进展不同阶段的直接影响的必要性。
Glucocorticoids are commonly used to prevent chemotherapy-induced nausea and vomiting despite a lack of understanding of their direct effect on cancer progression. Recent studies suggest that glucocorticoids inhibit cancer cell migration. However, this action has not been investigated in estrogen receptor (ER)-negative breast tumour cells, although activation of the glucocorticoid receptor (GR) is associated with a worse prognosis in ER-negative breast cancers. In this study we have explored the effect of glucocorticoids on the migration of the ER-negative MDA-MB-231 human breast tumour cell line and the highly metastatic MDA-MB-231-HM.LNm5 cell line that was generated through in vivo cycling. We show for the first time that glucocorticoids inhibit 2- and 3-dimensional migration of MDA-MB-231 cells. Selection of cells for high metastatic potential resulted in a less migratory cell phenotype that was resistant to regulation by glucocorticoids and showed decreased GR receptor expression. The emergence of glucocorticoid resistance during metastatic selection may partly explain the apparent disparity between the clinical and in vitro evidence regarding the actions of glucocorticoids in cancer. These findings highlight the highly plastic nature of tumour cells, and underscore the need to more fully understand the direct effect of glucocorticoid treatment on different stages of metastatic progression.