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Semin Thromb Hemost 2010; 36(3): 321-331
DOI: 10.1055/s-0030-1253454
© Thieme Medical Publishers

Heterogeneity of the Tumor Vasculature

Janice A. Nagy1 , Sung-Hee Chang1 , 2 , Shou-Ching Shih1 , Ann M. Dvorak1 , Harold F. Dvorak1
  • 1Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and the Departments of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
  • 2Department of Pathology and Laboratory Medicine, Weil Cornell Medical School, New York, New York
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Publication History

Publication Date:
20 May 2010 (online)

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ABSTRACT

The blood vessels supplying tumors are strikingly heterogeneous and differ from their normal counterparts with respect to organization, structure, and function. Six distinctly different tumor vessel types have been identified, and much has been learned about the steps and mechanisms by which they form. Four of the six vessel types (mother vessels, capillaries, glomeruloid microvascular proliferations, and vascular malformations) develop from preexisting normal venules and capillaries by angiogenesis. The two remaining vessel types (feeder arteries and draining veins) develop from arterio-venogenesis, a parallel, poorly understood process that involves the remodeling of preexisting arteries and veins. All six of these tumor vessel types can be induced to form sequentially in normal mouse tissues by an adenoviral vector expressing vascular endothelial growth factor. Current antiangiogenic cancer therapies directed at VEGF-A or its receptors have been of only limited benefit to cancer patients, perhaps because they target only the endothelial cells of the tumor blood vessel subset that requires exogenous VEGF-A for maintenance. A goal of future work is to identify therapeutic targets on tumor blood vessel endothelial cells that have lost this requirement.

KEYWORDS

Angiogenesis - arterio-venogenesis - tumors - vascular endothelial growth factor - VEGF-A

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Harold F DvorakM.D. 

Department of Pathology, Beth Israel Deaconess Medical Center

330 Brookline Avenue, RN227c, Boston, MA 02215

Email: hdvorak@bidmc.harvard.edu