Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor

Journal article


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Publication Details

Author list: Sckell A
Publisher: National Academy of Sciences
Publication year: 1998
Volume number: 95
Issue number: 18
Start page: 10820
End page: 10825
Number of pages: 6
ISSN: 0027-8424
Languages: English-Great Britain (EN-GB)


The sequence of events that leads to tumor vessel regression and the
functional characteristics of these vessels during hormone-ablation
therapy are not known. This is because of the lack of an appropriate
animal model and monitoring technology. By using in vivo microscopy and
in situ molecular analysis of the androgen-dependent Shionogi carcinoma
grown in severe combined immunodeficient mice, we show that castration
of these mice leads to tumor regression and a concomitant decrease in
vascular endothelial growth factor (VEGF) expression. Androgen
withdrawal is known to induce apoptosis in Shionogi tumor cells.
Surprisingly, tumor endothelial cells begin to undergo apoptosis before
neoplastic cells, and rarefaction of tumor vessels precedes the decrease
in tumor size. The regressing vessels begin to exhibit normal
phenotype, i.e., lower diameter, tortuosity, vascular permeability, and
leukocyte adhesion. Two weeks after castration, a second wave of
angiogenesis and tumor growth begins with a concomitant increase in VEGF
expression. Because human tumors often relapse following
hormone-ablation therapy, our data suggest that these patients may
benefit from combined anti-VEGF therapy.


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