Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential

Abstract

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.

All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells

“…Since it has been reported that the anti-inflammatory agent dexamethasone inhibits MMP-2 expression [ 27 , 29 ] and cancer cell migration [ 38 – 40 ], we examined the effect of dexamethasone on ATRA-induced MMP-2 secretion in THP-1 cells. The cells were pretreated with dexamethasone at different concentrations for 2 h, followed by ATRA treatment for 48 h. The culture supernatants were concentrated and subjected to western blot analysis.…”

Progesterone suppresses the invasion and migration of breast cancer cells irrespective of their progesterone receptor status - a short report

“…The non-essential role of PR that we observed in the inhibition of migration of breast cancer-derived cells in response to progesterone, specifically in the PR-negative MDA-MB-231, ZR-75-1 and BT-549 cells, may be mediated by interaction of progesterone with the glucocorticoid receptor (GR) or the membrane progesterone receptor (mPR), as has been reported before [ 22 , 24 , 25 ]. Of note, it has also been reported that treatment with glucocorticoids may similarly decrease the migration of PR-negative MDA-MB-231 cells [ 26 ], which suggests that redundant pathways may underlie the progesterone response in a PR-independent manner [ 27 ]. Consistent with these observations, we found that blocking PR by mifepristone prior to exposing the cells to progesterone did not rescue the effect of progesterone, suggesting that the progesterone-mediated suppression of migration in breast cancer cells is predominantly mediated in a PR-independent manner (Supplementary Fig.…”

Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

“…Prominent metabolic side effects of glucocorticoid treatment might be ascribed to transactivation of GRα 54 . In contrast, positive effects of glucocorticoids include reduced migration and a reduction in proteins associated with chemotherapy resistance in TNBC cells, which might be explained by transrepression of GRα [55][56][57] .…”