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 log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 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. ConclusionsIn 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.

Highlights

  • The hypercoagulable status is closely related to metastasis and a poor prognosis in cancer patients [1,2,3,4,5]

  • By constructing and comprehensively evaluating the effectiveness of in vivo and in vitro models, we provide powerful research tools to study the hypercoagulable status that is characterized by platelet activation in the context of promoting hematogenous metastasis in breast cancer

  • In our analysis of the decisive roles of the tumor-bearing period (TBP) and postoperative incubation period (PIP) in lung metastasis, we found that (1) when the TBP is too short, the tumor does not have time to undergo invasion and metastasis, which directly affects the success of metastasis; in contrast, when the TBP is too long, the tumor invades the surrounding tissue, which undoubtedly increases the difficulty of achieving effective surgical treatment

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Summary

Introduction

The hypercoagulable status is closely related to metastasis and a poor prognosis in cancer patients [1,2,3,4,5]. Accumulated research shows that hypercoagulability is a common complication of breast cancer and forms a vicious cycle with hematogenous metastasis [17]. 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. 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. 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

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