A Hypercoagulable Hematological Metastasis Breast Cancer Model

Abstract

Background. The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. Methods. Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. Results. The multiple linear regression model was constructed as $\log 10\left(\text{photon}\text{number}\right)=0.147\text{TBP}+0.14\text{PIP}+3.303$ ( $\text{TBP}\le 25$ and $\text{PIP}\le 17$ ) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. Conclusions. In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.