Circulating Tumor Cells: Does Ion Transport Contribute to Intravascular Survival, Adhesion, Extravasation, and Metastatic Organotropism?

Abstract

Survival in the circulation, extravasation from vasculature, and colonizing new tissues represent major steps of the metastatic cascade and pose a big challenge for metastasizing tumor cells. Tumor cells circulating in blood and lymph vessels need to overcome anoikis, cope with mechanical stimuli including shear stress, and defeat attacks by the immune system. Once adhered to the vessel wall, a circulating tumor cell (CTC) can trick the endothelial cells into loosening their intercellular junctions so that the endothelium becomes penetrable for the tumor cell. Since tumor cells tend to metastasize to predestinated target organs and tissues, called organotropism, the distribution of metastases is anything but random. The molecular-physiological mechanisms underlying CTC survival, extravasation, and organotropism are very likely to include the presence and activity of ion channels/transporters due to the latter's key function in cytophysiological processes. To date, a very limited number of studies explicitly show the involvement of ion transport. This review describes the contribution of ion channels and transporters to CTC survival, extravasation, and organotropism where known and possible. In addition, supposed connections between ion transport and CTC behavior are demonstrated and imply the potential to be therapeutically taken advantage of.