Combinations of common anticancer chemotherapeutics with synthetic glucocorticoids (GCs) are usually used to broaden the therapeutic range of main cytostatics and to diminish the side effects of chemotherapy. However, long-term GC administration may lead to the selection of resistant tumor subclones and the promotion of metastasis. GC effects are mediated by glucocorticoid receptor (GR), which regulating gene expression via DNA-dependent transactivation associated with side effects of GCs, and therapeutically important transrepression, negative interaction between GR and transcription factors.

The main aim of this study was to find out the molecular markers associated with GC-stimulated cell motility and migration potential of breast cancer cells.

Breast cancer cells with epithelial (MCF-7) and mesenchymal-like (MDA-MB-231) phenotype were used as model cells. Cells were treated with Dexamethasone for 24 h. Migration activity were observed in Boyden chamber assay. Expression of 84 specific genes associated with epithelial–mesenchymal transition and cell adhesion (encoding integrin, connexin, cadherin, caveolin, fibullin, desmocolin, interleukin and caveolin protein families) were evaluated by real time q-PCR.

In MCF-7 cells with low metastatic potential, GC induced decrease of claudin, integrin and caveolin family genes. In triple negative breast cancer cell line MDA-MB-231, activation of GR lead to significant decrease in the expression of genes encoding claudins and connexins. In addition, Dexamethasone promote MCF-7 and MDA-MB-231 migration through Boyden chamber.

Thus, we showed that GCs stimulate the invasion and metastasis of breast cancer cells independently from their phenotypes. Moreover, we determined the most significant genetic markers of GC-associated loss of adhesion in breast cancer cells.

Work was partial supported by RSCF (17-75-20124) and RFBR (16-04-01410, 15-04-04006).