Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenes...

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Autores principales:	Viviana P Montecinos, Alejandro Godoy, Jennifer Hinklin, R Robert Vethanayagam, Gary J Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2f503e4fc49c4af68079742c4460defb
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spelling	oai:doaj.org-article:2f503e4fc49c4af68079742c4460defb2021-11-18T07:29:06ZPrimary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.1932-620310.1371/journal.pone.0029623https://doaj.org/article/2f503e4fc49c4af68079742c4460defb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22303438/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts.Viviana P MontecinosAlejandro GodoyJennifer HinklinR Robert VethanayagamGary J SmithPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29623 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Viviana P Montecinos Alejandro Godoy Jennifer Hinklin R Robert Vethanayagam Gary J Smith Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
description	Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts.
format	article
author	Viviana P Montecinos Alejandro Godoy Jennifer Hinklin R Robert Vethanayagam Gary J Smith
author_facet	Viviana P Montecinos Alejandro Godoy Jennifer Hinklin R Robert Vethanayagam Gary J Smith
author_sort	Viviana P Montecinos
title	Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
title_short	Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
title_full	Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
title_fullStr	Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
title_full_unstemmed	Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
title_sort	primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2f503e4fc49c4af68079742c4460defb
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Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.

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