Novel in vitro perfusion model to study the interaction between coagulation and blood-borne metastasis

The association between cancer and hemostasis has long been studied in cell culture, animal models, and cancer patients developing thrombosis. The variety of biologic mechanisms involved in malignancy and metastasis makes the understanding of the relative importance of each mechanism difficult. We have developed a novel in vitro perfusion model that allows for the isolated study of the interactions between tumor cells and components of the hemostatic system under normal physiologic conditions. Segments of denuded umbilical cord or saphenous vein are cut longitudinally and mounted in a perfusion chamber under sterile conditions. Human breast cancer cells are perfused for 24 h under venous flow conditions with either whole blood (WB), platelet-rich plasma (PRP), platelet-poor plasma (PPP), or serum. Tissue samples are fixed and stained with hematoxylin and eosin as well as with pan-cytokeratin. Morphometric analysis is performed to quantify cancer cell adhesion. With PRP, this model maintains normal human physiologic conditions for the duration of the experiment. It differentiates between previously characterized high and low metastatic breast cancer cell lines. In addition, different vein tissue types do not alter tumor cell attachment. This model appears to be an accurate representation of the pathophysiology of in vivo metastasis. This model may serve as a useful bridge between cell culture studies and animal models. It may be a useful tool to elucidate the role of selected hemostatic systems in blood-borne metastasis and may potentially serve as a screening tool for the development of antimetastatic pharmaceutical agents.