Endothelium and cancer metastasis: Perspectives for antimetastatic therapy

Endothelial cells accompany the malignant cancer cell in almost every stage of metastatic process which includes: infiltration of tumor cells into the neighboring tissue, transmigration through endothelium (intravasation), survival in the blood stream, and extravasation followed by colonization of the target organ. The blood vessels within the tumor are heterogeneous, highly permeable, and chaotically branched therefore often described as abnormal or dysfunctional. These abnormalities are common for all components of the vessel wall and result from the activity of such factors as hypoxia and chronic growth factor stimulation. In this review, we focus not only on the distinctions in terms of the characteristic and function of tumor endothelial cells (TEC) as compared to normal endothelial cells (NEC), but also on all of these metastasis steps, which are accompanied by endothelial mediated mechanisms. Moreover, some therapeutic approaches directly or indirectly targeting the endothelium are discussed.