Introduction. Glucocorticoids are used as an adjuvant treatment for breast cancer patients undergoing chemotherapy, due to their anti-emetic properties. However, they are known to have diverse effects on both the tumour and surrounding microenvironment. We have previously shown that dexamethasone, a commonly used glucocorticoid, slows the migration of MDA-MB-231 cells. Breast cancer mortality commonly results from metastatic disease. Therefore, we have utilised a highly metastatic MDA-MB-231 cell subline (HM) 1 , exploring both the basal migratory phenotype and glucocorticoid influence.
Methods. Parental MDA-MB-231 cells were obtained from American Type Culture Collection (ATCC). HM MDA-MB-231 cells were generated from a population of cells selected by 6 cycles of transplanting spontaneous MDA-MB-231 pulmonary metastases to the mammary fat pad 1 . The resulting cells therefore had high pulmonary metastasis potential. Scrape wound healing and Boyden chamber assays used MDA-MB-231 cells incubated with 1% fetal calf serum (FCS), following pre-treatment with dexamethasone (100nM). Images of the scrape wound were taken every 30min for 16 hours and the number of migrated cells through polycarbonate membranes (8mm pores) was counted.
Results. MDA-MB-231 HM cells showed reduced FCS-stimulated migration compared to parental MDA-MB-231 ATCC cells in the Boyden chamber assay (ATCC: 91±12, HM: 57±9 cells, n=4). There was no difference in FCS-induced migration in the scrape wound healing assay (ATCC: 142±20%, HM: 124±18% control migration, n=3). However, addition of dexamethasone failed to inhibit FCS-induced MDA-MB-231 HM cell migration in each assay.
Discussion. The widespread use of glucocorticoids in breast cancer patients raises interest in observations beyond their indication as an anti-emetic. We have previously observed that dexamethasone may have a beneficial effect, slowing the migration of breast cancer cells. However, differing glucocorticoid responses of primary MDA-MB-231 cells and those propagated from pulmonary metastasis suggest that the impact of glucocorticoids may be more complex, involving cell origin and stage of tumour progression.