Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation
Date
2021-04-16
Authors
Xulu, Kutlwano R.
Augustine, Tanya N.
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Thromboembolic complications are a leading cause of morbidity and mortality in cancer
patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation,
so the application of antiplatelet strategies to oncology warrants further investigation. This
study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or
atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced
hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast
cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h.
Hypercoagulation was indicated by thrombin production and platelet activation (morphological
and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT)
was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were
evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet
therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent
hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate
tumour aggression were noted between breast cancer cell lines, and this may be an important
consideration in the clinical management of subphenotypes of luminal phenotype breast cancer.
Further investigation is needed before this treatment modality (combined hormone and antiplatelet
therapy) can be considered for managing tumour associated-thromboembolic disorder.
Description
Keywords
Breast cancer, Hypercoagulation, Aspirin, Clopidogrel, Atopaxar, Anastrozole, Platelet activation, Thrombin activity, Tumour survival
Citation
Xulu K. R. and Augustine T. N. Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation. Vol. 22, International Journal of Molecular Sciences. 2021. DOI: 10.3390/ijms22084153