Tumor endothelial cells

Abstract

The vascular endothelium is a dynamic cellular "organ" that controls passage of nutrients into tissues, maintains the flow of blood, and regulates the trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth factor stimulation result in endothelial dysfunction. For example, tumor blood vessels have irregular diameters; they are fragile, leaky, and blood flow is abnormal. There is now good evidence that these abnormalities in the tumor endothelium contribute to tumor growth and metastasis. Thus, determining the biological basis underlying these abnormalities is critical for understanding the pathophysiology of tumor progression and facilitating the design and delivery of effective antiangiogenic therapies.

Figure 1.

Abnormalities in tumor endothelial cells. In a normal blood vessel (shown at left) a monolayer of endothelial cells form tight junctions with one another without overlapping at the margins. In contrast, TECs branch and sprout excessively resulting in a defective endothelial monolayer and loss of their normal barrier function. These branches may extend across the lumen and overlap with neighboring endothelial cells. Changes in endothelial shape result in intercellular gaps or holes that leak fluid, blood, and fibrin into the surrounding tissue.

Figure 2.

A reductionist versus contemporary view of tumor endothelium. In a reductionist view, all of the endothelial cells lining a tumor blood vessel are homogeneous and perhaps derived by spouting or simple cooption of nearby vessels. In the contemporary view, TECs are heterogeneous and derived from multiple sources. A composite tumor blood vessel is shown in which the endothelium may be derived by cooption or sprouting, from endothelial progenitors localized in the vessel wall, from tumor cells masquerading as endothelial cells, from marrow-derived endothelial progenitors, and from unexpected sources including transdifferentiated myeloid and mesenchymal lineage cells. Plasticity and a multisource origin may contribute to tumor blood vessel abnormalities and allow tumor vessels to evade antiangiogenic therapies.