![]() The size of the openings (<2 μm in diameter) between endothelial cells examined by scanning electron microscopy fits the functional measurements of the pore cutoff size of tumor vessels. The cells also have loose interconnections and focal intercellular openings, which are likely to be responsible for much of the vessel leakiness. Endothelial cells of some tumor vessels overlap one another, have luminal projections, and give rise to abluminal sprouts. The cells are disorganized and irregularly shaped. ![]() Endothelial cells, although present on most if not all tumor vessels, do not form a normal monolayer and thus do not have a normal barrier function (1, 3). Although some reports suggest that tumor vessels lack endothelial cells, pericytes (mural cells), or basement membrane, recent work indicates that all of these components are present but abnormal (1, 2). Peter Baluk (University of California, San Francisco, CA), who studies the morphological abnormalities of tumor vessels, portrayed the structural irregularity, heterogeneity, and leakiness of tumor vessels as bizarre hallmarks of a propensity to break all of the rules of normal blood vessel construction. Even large-caliber vessels have thin, leaky walls. Most tumor vessels have an irregular diameter and an abnormal branching pattern and do not fit well into the usual classification of arterioles, capillaries, or venules. New research tools such as intravital measurements of tumor blood flow and vessel leakiness, in vivo phage display, magnetic resonance imaging, and use of selective angiogenesis inhibitors will contribute to this understanding. The group concluded that a more complete understanding of the basic biology of tumor vessels will be necessary to fully appreciate the consequences of vessel leakiness in cancer. The participants discussed the cellular basis of tumor vessel leakiness, endothelial barrier function of blood vessels, monitoring tumor vessel leakiness, mediators of endothelial leakiness, consequences of tumor vessel leakiness, genomic analysis of vascular targets, targeting drugs to tumor vessels, and therapeutic manipulation of tumor vessels. The meeting was the first of its kind focused on the significance of blood vessel leakiness in tumors. Sixteen experts in the fields of cancer biology and vascular biology gathered at the William Guy Forbeck “Focus on the Future” Conference to discuss this topic. The leakiness of tumor vessels is well documented in experimental tumor models and in human cancer, but the mechanism is poorly understood, as are the implications to the rate of cancer growth, predisposition to metastasis, and delivery of macromolecular therapeutics to tumor cells. Despite major advances in the field of tumor angiogenesis, relatively little attention has been paid to the permeability of blood vessels in tumors.
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