DOI: 10.1073/pnas.95.18.10820. Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor

Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor

10.1073/pnas.95.18.10820

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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.

Bibliography

Jain, R. K., Safabakhsh, N., Sckell, A., Chen, Y., Jiang, P., Benjamin, L., Yuan, F., & Keshet, E. (1998). Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor. Proceedings of the National Academy of Sciences, 95(18), 10820â10825.

Authors 8

Rakesh K. Jain (first)
Nina Safabakhsh (additional)
Axel Sckell (additional)
Yi Chen (additional)
Ping Jiang (additional)
Laura Benjamin (additional)
Fan Yuan (additional)
Eli Keshet (additional)

References 25 Referenced 300

Moon W.-C. Choi I. R. & Moon S. Y. (1997) J. Urol. Suppl. 157 223. (10.1016/S0168-9525(97)01093-7)
I B J K Joseph, J D Nelson, I S R Denmeade, J T Isaacs Clin Cancer Res 3, 2507–2512 (1997). / Clin Cancer Res by Joseph I B J K (1997)
10.1002/1097-0142(19930501)71:9<2782::AID-CNCR2820710916>3.0.CO;2-Z
10.1507/endocrj.41.709
10.1016/0167-4889(95)90410-I
M Leunig, F Yuan, M D Menger, Y Boucher, A E Goetz, K Messmer, R K Jain Cancer Res 52, 6553–6560 (1992). / Cancer Res by Leunig M (1992)
10.1073/pnas.93.25.14765
10.1038/nm0996-992
10.1038/nm1095-1024
10.1038/359843a0
H G Augustin, K Braun, I Telemenakis, U Modlich, W Kuhn Am J Pathol 147, 339–351 (1995). / Am J Pathol by Augustin H G (1995)
U Modlich, F J Kaup, H G Augustin Lab Invest 74, 771–780 (1996). / Lab Invest by Modlich U (1996)
10.1073/pnas.94.16.8761
10.1038/380435a0
10.1038/380439a0
10.3109/10739689709146803
10.1007/978-3-0348-9006-9_10
10.1073/pnas.95.8.4607
10.1046/j.1523-1747.1998.00262.x
H Yoshiji, S R Harris, U P Thorgeirsson Cancer Res 57, 3924–3928 (1997). / Cancer Res by Yoshiji H (1997)
A K Gosh, D B Shanker, G M Shackleford, K Wu, A T’Ang, G J Miller, J Zhang, P Roy-Burman Cell Growth Differ 7, 1425–1434 (1996). / Cell Growth Differ by Gosh A K (1996)
10.1038/359845a0
10.1210/edrv.18.1.0287
E F Haran, A F Maretzek, I Goldberg, A Horowitz, H Degani Cancer Res 54, 5511–5514 (1994). / Cancer Res by Haran E F (1994)
A Gagliardi, D C Collins Cancer Res 53, 533–535 (1993). / Cancer Res by Gagliardi A (1993)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5 p.m.)
Indexed	2 months ago (June 26, 2025, 2:42 p.m.)
Issued	27 years ago (Sept. 1, 1998)
Published	27 years ago (Sept. 1, 1998)
Published Online	27 years ago (Sept. 1, 1998)
Published Print	27 years ago (Sept. 1, 1998)

Funders 0

None

BibTeX

@article{Jain_1998, title={Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.18.10820}, DOI={10.1073/pnas.95.18.10820}, number={18}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Jain, Rakesh K. and Safabakhsh, Nina and Sckell, Axel and Chen, Yi and Jiang, Ping and Benjamin, Laura and Yuan, Fan and Keshet, Eli}, year={1998}, month=sep, pages={10820–10825} }

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