title: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ebony R
authors.initials: ER
authors.lastname: Fietz
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Keenan
authors.affiliation: Health and Biomedical Informatics Centre, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Guillermo
authors.initials: G
authors.lastname: López-Campos
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Cameron N
authors.initials: CN
authors.lastname: Johnstone
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Trudi
authors.initials: T
authors.lastname: Harris
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D011960:Receptors, Estrogen