Advancing Tissue Factor-targeted Therapy for Osteosarcoma via Understanding its Role in the Tumor Microenvironment.

Coagulation activation is associated with cancer progression and morbidity. Recently, mechanisms through which coagulation proteases drive the tumor microenvironment (TME) have been elucidated. This study aims to develop a new strategy dependent on the coagulation system for treating osteosarcoma (OS). We focused on tissue factor (TF), the main initiator of the extrinsic coagulant pathway, as a target for OS treatment. It was found that cell surface-TF, TF-positive extracellular vesicles, and TF-positive circulating tumor cells could drive progression, metastasis, and TME in carcinomas, including OS. Thus, targeting tumor-associated coagulation by focusing on TF, the principle catalyst of the extrinsic pathway, TF is a promising strategy treatment for OS.