The vascular endothelium comprises of a layer of thin, flattened cells lining the inside surfaces of blood vessels and is a major regulator in many homeostatic and pathophysiologic mechanisms. In inflammation and injury
Detachment & x Vessel Penetration
Figure 1 A schematic reproduction of the metastasis process. Tumor cells first have to detach from the primary tumor, invade the blood circulation, subsequently adhere to the endothelium within a distant organ and finally invade and multiply to form a metastasis. (see color insert)
the endothelium is activated. The activation of endothelial cells leads to induction of adhesion molecules and the release of mediators, such as proinflammatory cytokines, chemokines, and reactive oxygen species. These processes lead to migration of inflammatory cells to the wounded or inflamed site. The vasculature constitutes the primary route by which tumor cells disseminate to distant sites. Interactions between circulating tumor cells and the endothelium significantly influence the outcome of the metastatic process.
Selectins, integrins, cadherins, immunoglobulins, and other unclassified molecules have been demonstrated to govern the adhesive interactions between tumor cells and the endothelium, analogous to their ability to effect localization of leukocytes at sites of inflammation. Some of these adhesion molecules are expressed constitutively and appear to have organ specificity in their distribution. Others are inducible and under the influence of environmental mediators such as the proinflammatory cytokines.
There are macrovascular endothelial cells surrounding large blood vessels, such as arteries and veins, and microvascular endothelial cells surrounding small vessels, the arterioles, venules, and capillaries. Microvascular and macrovascular cells are heterogeneous as microvascular cells react differently to stimuli compared to macrovascular endothelial cells. Differences exist not only between macro-vascular and microvascular endothelial cells, but also between endothelial cells from different vascular beds. Each organ has its own microenvironment with different characteristics, such as a different pattern of endothelial adhesion molecules, reacting particularly to stimuli.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.