Glucocorticoids Enhance Metastatsis And Tumorigenicity In A Triple Negative Breast Cancer Cell Line

Abstract Glucocorticoid (GC) is commonly co-administered with chemotherapy to prevent drug-induced allergic reaction, nausea, and vomiting. We have previously reported that GC may affect growth and chemosensitivity of carcinoma cells via diverse mechanisms (Lung Cancer 2006, 53:303-10; J Endocrinol 2006,188:311-9; World J Gastroenterol. 2005, 28:6373-80). Along this line, we further explored the effect of GC on breast cancer cells. Treatment of dexamethasone (DEX) resulted in early axillary lymph node metastases, and increased the number of lung and liver metastases in an orthotopic xenograft model of a triple negative breast cancer cell line (MDA-MB-231) in nude mice (BALB/cAnN.Cg-Foxn1nu/CrlNarl). In tail vein injection assay of cancer metastasis, treatment of DEX dramatically enhanced the lung metastatic potential of a lung-seeking sub-clone, MDA-MB-231-Lu2 (derived from lung metastasis of MDA-MB-231 cells after two in vivo passages in nude mice using intracardiac injection). To explore the mechanism of GC-induced metastasis of breast cancer cells, we performed several in vitro studies. While DEX does not affect the proliferation rate of MDA-MB-231 cells according to MTT assay, treatment of DEX enhanced the tumorigenicity of the cells according to soft agar tumor sphere formation assay. On the other hand, treatment of DEX decreased tumorigenicity in two non-TNBC cell lines, MCF7 and T47D cells. Using quantitative polymerase chain reaction and Western blots assay, we found that treatment of DEX increased the expression of Slug, an epithelial-to-mesenchymal transition (EMT) related gene, and angiopoietin-like 4 (ANGPTL4), an important lung metastasis related gene, in MDA-MB-231 cells, but not in MCF7 and T47D cells. Using transwell migration/invasion assay (with or without matrigel above the membrane), we found that the conditioned medium of DEX-treated lung and liver tissues of mice attracted the MDA-MB-231 cells and promote migration/invasion. In conclusion, GC enhances metastasis and tumorigenicity in MDA-MB-231 cells, a triple negative breast cancer cell line. Whether GC may have a detrimental clinical effect on this subtype of breast cancer patients need to be verified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 454. doi:1538-7445.AM2012-454