Transport of Water and Solutes Across Endothelial Barriers and Tumor Cell Adhesion in the Microcirculation

Understanding where and how water and solutes transport through the microvessel wall at cellular and molecular levels is crucial for developing strategies to deliver therapeutic drugs and to treat various diseases, including tumor metastasis. The vascular endothelium forming the microvessel wall is the principal barrier to, and regulator of, material exchange between circulating blood and body tissues. The ultrastructural pathways and the mechanisms by which endothelial cells and the cleft between the cells (interendothelial cleft) modulate microvessel permeability to water and solutes have been long-standing unresolved questions in microvascular transport since the early 1950s. In light of recent experimental studies on individual perfused microvessels and intact microvascular beds, this chapter addresses these classical questions in a multidisciplinary approach. The mathematical models which describe the transport of water and solutes through the interendothelial cleft and in the surrounding tissue are introduced. These models, combined with experimental results from in vivo animal studies and electron microscopic observations, are used to evaluate the role of the endothelial surface glycocalyx, the junction strand geometry in the interendothelial cleft and the surrounding extracellular matrix (ECM) and tissue cells, as the determinants of permeability properties. The endothelial surface glycocalyx layer of peripheral microvessels serves as a molecular filter to prevent the loss of macromolecules from the blood circulation, and thus keeps us in good health. In addition to this glycocalyx layer and the interendothelial tight junctions, the ECM of the basement membrane and the wrapping astrocyte processes in the blood-brain barrier of the cerebral microvessel provide further protection for the central nervous system. Under pathological conditions, the interendothelial cleft is suggested to be the pathway for the transport of high molecular weight plasma proteins, leukocytes and tumor cells across microvessel walls. Therefore, another part of this chapter demonstrates how the microvascular permeability, hydrodynamic factors, microvascular geometry and cell adhesion molecules affect tumor cell adhesion in the microcirculation. The role of integrin signaling during tumor cell adhesion is also discussed.