Intravascular cell-to-cell adhesive interactions and bone metastasis

Metastatic cancer spread to bones, causing intractable pain, pathological fractures, spinal cord compression, and ultimately death, represents massive clinical problem. Intravascular cell-to-cell heterotypic (between cancer and other types of cells) and homotypic (between cancer cells) adhesive interactions, leading to the establishment of metastatic deposits in bone marrow vasculature, represent important rate-limiting steps in bone metastasis. In this review, we discuss molecular and cellular mechanisms underpinning metastasis-associated intravascular cell-to-cell adhesive interactions, their role in a multi-step metastatic cascade, and a potential for therapeutic targeting of early metastasis-associated adhesive events.