School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, 2193, Parktown, Johannesburg, South Africa.
J Thromb Thrombolysis. 2022 Oct;54(3):401-410. doi: 10.1007/s11239-022-02690-w. Epub 2022 Aug 6.
Anastrozole is commonly used for the treatment of oestrogen receptor (ER)-positive breast cancer but can increase thromboembolic risk. It is unclear if ER presentation is associated with platelet-mediated hypercoagulation. We investigated the relationship between hypercoagulation and ERα and ERβ expression in breast cancer cell lines under Anastrozole treatment.
In Model 1, MCF-7 or T47D cancer cells were treated with Anastrozole, then exposed to whole blood and platelet-rich plasma, modelling platelet engagement in the tumour bed. In Model 2, blood components were treated with Anastrozole, then exposed to cancer cells, modelling circulatory effects in the vasculature. Hypercoagulation was assessed as a combined function of thrombin activity, platelet CD62P and CD63 expression, and corresponding platelet ultrastructure. Tumour ERα and ERβ were immunolocalised and following quantification assessed for correlation with hypercoagulatory parameters.
Anastrozole enhanced hypercoagulation in both Models and cell lines. T47D cells induced more distinct features of hypercoagulation and responded by heightening ERβ expression and sustaining expression of ERα, indicative of a more aggressive phenotype. Post-exposure to cell lines, CD62P and CD63 expression correlated, but this was not maintained following Anastrozole treatment. Substantive correlations could not be found explaining the changes in ER expression and hypercoagulatory parameters, indicating unknown causative factors.
These results provide basic science evidence showing that the hypercoagulatory effects induced by Anastrozole treatment may be related to the tumour subphenotype. Clinical studies are required to determine whether tracking of hypercoagulatory parameters may hold value in describing subphenotypic alterations or metastatic potential during tumour progression.
阿那曲唑常用于治疗雌激素受体（ER）阳性乳腺癌，但会增加血栓栓塞风险。目前尚不清楚 ER 表达是否与血小板介导的高凝状态有关。我们研究了阿那曲唑治疗下乳腺癌细胞系中高凝状态与 ERα 和 ERβ 表达之间的关系。
在模型 1 中，MCF-7 或 T47D 癌细胞用阿那曲唑处理，然后暴露于全血和富含血小板的血浆中，模拟血小板在肿瘤床中的参与。在模型 2 中，血液成分用阿那曲唑处理，然后暴露于癌细胞，模拟循环系统在血管中的作用。高凝状态通过凝血酶活性、血小板 CD62P 和 CD63 表达的综合功能以及相应的血小板超微结构来评估。肿瘤 ERα 和 ERβ 进行免疫定位，并在量化后评估与高凝参数的相关性。
阿那曲唑增强了两种模型和细胞系中的高凝状态。T47D 细胞诱导出更明显的高凝特征，并通过增强 ERβ 表达和维持 ERα 的表达来响应，这表明其具有更具侵袭性的表型。暴露于细胞系后，CD62P 和 CD63 表达相关，但在阿那曲唑处理后并未维持。无法找到解释 ER 表达和高凝参数变化的实质性相关性，表明存在未知的因果因素。
这些结果提供了基础科学证据，表明阿那曲唑治疗诱导的高凝状态可能与肿瘤亚表型有关。需要进行临床研究以确定跟踪高凝参数是否在描述肿瘤进展过程中的亚表型改变或转移潜力方面具有价值。
