Tumor Metastasis in the Microcirculation

Tumor cell metastasis through blood circulation is a complex process and is one of the great challenges in cancer research as metastatic spread is responsible for ∼90% of cancer-related mortality. Tumor cell intravasation into, arrest and adhesion at, and extravasation from the microvessel walls are critical steps in metastatic spread. Understanding these steps may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to and regulators of the material exchange between circulating blood and body tissues. The cleft between adjacent endothelial cells is the principal pathway for water and solute transport through the microvessel wall in health. This cleft has been found to be the location for tumor cell adhesion and extravasation. The blood flow-induced hydrodynamic factors such as shear rates and stresses, shear rate, and stress gradients, as well as vorticities, especially at the branches and turns of microvasculatures, also play important roles in tumor cell arrest and adhesion. This chapter first reports the current advances from in vivo animal studies and in vitro culture cell studies to demonstrate how the endothelial integrity or microvascular permeability, hydrodynamic factors, microvascular geometry, cell adhesion molecules, and surrounding extracellular matrix affect critical steps of tumor metastasis in the microcirculation. One addition of this updated chapter shows the role of glycocalyx at tumor cells in tumor cell metastasis. Another addition describes a new in vitro 3D-microchannel model for tumor metastasis in the microcirculation.