Platelets in Hematogenous Breast Cancer Metastasis: Partners in Crime

ABSTRACT

Distant metastasis is the primary driver of breast cancer-associated mortality, and research into the mechanisms underlying hematogenous tumor cell dissemination could give rise to the development of novel and more effective therapeutic agents and strategies. Platelets are activated directly by tumor cell interaction and indirectly by tumor-secreted factors to trigger platelet aggregation, degranulation, and the subsequent release of pro-tumorigenic factors. Platelet presence within the primary tumor, bloodstream, and metastatic sites allows for continuous exposure of breast cancer cells to these factors, making platelets a powerful partner in tumor cell dissemination. Platelet-tumor cell crosstalk contributes to hematogenous breast cancer metastasis by providing physical and biochemical support to metastasizing cells via mechanisms including protection from shear forces, anoikis, and immune attack, and enhancement of angiogenesis, migration, and pro-tumorigenic inflammation. Here, we review platelets and their many benefits to metastatic breast cancer, their role in facilitating paraneoplastic thrombosis, and current research regarding their potential as a breast cancer therapeutic target.