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Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal
Laura E. Benjamin, … , Dov Pode, Eli Keshet
Laura E. Benjamin, … , Dov Pode, Eli Keshet
Published January 15, 1999
Citation Information: J Clin Invest. 1999;103(2):159-165. https://doi.org/10.1172/JCI5028.
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Article

Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal

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Abstract

Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.

Authors

Laura E. Benjamin, Dragan Golijanin, Ahuva Itin, Dov Pode, Eli Keshet

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Figure 2

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Most blood vessels in glioblastoma multiforme are immature. (a and b) Se...
Most blood vessels in glioblastoma multiforme are immature. (a and b) Serial sections of a glioblastoma multiforme tumor stained with anti-vWF (a) and with anti–α-SMA (b) showing only few α-SMA–positive vessels (arrows). (c) Four glioblastoma specimens were serially stained for α-vWF and α-SMA. Vessels larger than capillaries were scored (between 58 and 212 for each specimen), and the percentage of α-SMA–positive vessels is presented (averaging 19%; SEM = 8.3%). For comparison, vessels of a normal adult brain (rat) were also evaluated for the percentage of α-SMA–positive vessels (average of six high-power fields was 95%; SEM = 3%). vWF, von Willebrand factor.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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