Ex vivo interaction between blood components and hormone-dependent breast cancer cells induces alterations associated with epithelial-mesenchymal transition and thrombosis. (3rd May 2020)

• Record Type: Journal Article
• Authors: Augustine, T. N.; Pather, K.; Mak, D.; Klonaros, D.; Xulu, K.; Dix-Peek, T.; Duarte, R.; van der Spuy, W. J.
• Is Part Of: Ultrastructural pathology. Volume 44:Number 3(2020)
• Page Start: 262
• Page End: 272
• Publication Date: 2020-05-03
• Subjects: Hormone-dependent breast cancer -- thrombosis -- platelet -- transforming growth factor (TGF-β1) -- epithelial-mesenchymal transition; Pathology, Cellular -- Periodicals; Ultrastructure (Biology) -- Periodicals; Diagnosis, Electron microscopic -- Periodicals; Microscopy, Electron; Pathology; 616.07582
• DOI: 10.1080/01913123.2020.1749197
• Languages: English
• ISSNs: 0191-3123

Abstract

ABSTRACT: The prevalence of breast cancer is steadily increasing with metastasis and thromboembolic complications identified as the most common causes of death. The acquisition of an aggressive phenotype by hormone-dependent breast cancers is mediated by Transforming Growth Factor Beta 1 (TGF-β1 ) expression and is associated with epithelial-mesenchymal transition (EMT) and, potentially, increased propensity for thrombosis. We investigated this phenomenon by assessing the effect of platelet-rich plasma (PRP) and whole blood (WB) on parameters of EMT and hypercoagulation in vitro . MCF-7 breast cancer cells were cultured under standard conditions, followed by co-culture with PRP or WB. Cells were processed for real-time PCR ( TGF-β1 and vimentin ), electron microscopy or immunocytochemistry (TGF-β1 ). Micrographs were qualitatively assessed, and real-time PCR data analyzed with PAST Statistical Software. The addition of blood components heightened TGF-β1 immunolocalization and significantly increased corresponding gene expression. Both PRP and WB significantly increased vimentin expression and induced a shape change from a typical epithelial phenotype to a spindle-shape morphology, indicative of EMT. Fibrin fiber, network and plaque formation indicated a hypercoagulatory environment. The results thus show that in preparation for hematogenous metastasis, hormone-dependent breast cancer cells assume an aggressive phenotype associated with EMT, simultaneously increasing the propensity for the formation of thrombo-emboli.