Perspectives: Interplay Between Melanoma Regulated Fibrin and Receptor Mediated Adhesion Under Shear Flow

Metastasis is a complex process that ultimately results in secondary tumor formation, posing a threat to patient survival. However, the mechanisms by which circulating tumor cells adhere to the endothelium and escape from the vasculature are not fully understood. To bind to the endothelium, tumor cells must resist the shear forces induced by flow, largely through receptor-mediated cell–cell interactions. Tumor cells are able to manipulate the metastatic site microenvironment via thrombin and soluble fibrin (sFn) regulation, impacting both coagulation and cell adhesion processes. Thus, thrombosis may be recognized as a prognostic indicator of highly metastatic tumors. Herein, we describe some correlations between the metastatic potential of tumor cells and coagulation. This perspectives review focuses on the role of sFn in melanoma-endothelial adhesions under shear conditions. Specifically, sFn serves as a divalent ligand for αvβ3, CD11b/CD18 (αmβ2, Mac-1), and intercellular adhesion molecule-1 (ICAM-1) transmembrane receptors. The cross-linking role of sFn is examined in relation to host leukocytes, in particular, the polymorphonuclear neutrophil (PMN)-mediated adhesions of melanoma cells to the endothelium. These results have shed light on the significant interplay between melanoma cells, PMNs, and the endothelium under shear conditions, which is key in the struggle to better diagnose and treat melanoma metastases.