Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation.
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.
['Xulu|Kutlwano R|KR|', 'Augustine|Tanya N|TN|']
D000328:Adult D000077384:Anastrozole D018931:Antineoplastic Agents, Hormonal D001241:Aspirin D001777:Blood Coagulation D001943:Breast Neoplasms D002478:Cells, Cultured D000077144:Clopidogrel D004347:Drug Interactions D058750:Epithelial-Mesenchymal Transition D005260:Female D006801:Humans D007097:Imines D061986:MCF-7 Cells D010975:Platelet Aggregation Inhibitors D011725:Pyridines D013917:Thrombin D019851:Thrombophilia
anastrozole breast cancer hypercoagulation aspirin clopidogrel atopaxar platelet activation thrombin activity tumour survival