Biomedical Engineering Reference
In-Depth Information
Chapter 4
Microvascular Permeability and Tumor
Metastasis
Bingmei M. Fu
Abstract
Angiogenesis and microvascular hyperpermeability are two critical
processes for tumor growth and metastasis. Although various anti-angiogenic
therapies have been postulated to inhibit tumor growth and intravasation since the
early 1970s, strategies targeting at microvascular hyperpermeability to prevent
tumor cell adhesion and extravasation have not been well developed. The 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
(interendothelial cleft) is the principal pathway for water and solute transport
through the microvessel wall in health. It is also suggested to be the pathway for
high molecular weight plasma proteins, leukocytes, and tumor cells across
microvessel walls in disease. Thus this review first introduces the mathematical
models for transport of water and solutes through the interendothelial cleft.
These models, combined with the experimental results from in vivo animal studies
and electron microscopic observations, are used to evaluate the role of the endothe-
lial surface glycocalyx, the junction strand geometry in the interendothelial cleft,
and the surrounding extracellular matrix and tissue cells, as the determinants of
microvascular transport. The second part of the review demonstrates how changes
in microvascular permeability and blood flow affect tumor cell adhesion in in vivo
and in vitro model systems. The role of integrin signaling during tumor cell
adhesion is also discussed.
B.M. Fu (
*
)
Department of Biomedical Engineering, The City College of the City University of New York,
160 Convent Avenue, New York, NY 10031, USA
e-mail:
fu@ccny.cuny.edu
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