Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.

Metastatic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endo...

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Autores principales:	Rodrigo Fernández-Periáñez, Irene Molina-Privado, Federico Rojo, Irene Guijarro-Muñoz, Vanesa Alonso-Camino, Sandra Zazo, Marta Compte, Ana Alvarez-Cienfuegos, Angel M Cuesta, David Sánchez-Martín, Ana M Alvarez-Méndez, Laura Sanz, Luis Alvarez-Vallina
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ee65d3045ff4059abeaf2b357359dba
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spelling	oai:doaj.org-article:5ee65d3045ff4059abeaf2b357359dba2021-11-18T09:00:31ZBasement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.1932-620310.1371/journal.pone.0072957https://doaj.org/article/5ee65d3045ff4059abeaf2b357359dba2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23951338/?tool=EBIhttps://doaj.org/toc/1932-6203Metastatic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention.Rodrigo Fernández-PeriáñezIrene Molina-PrivadoFederico RojoIrene Guijarro-MuñozVanesa Alonso-CaminoSandra ZazoMarta CompteAna Alvarez-CienfuegosAngel M CuestaDavid Sánchez-MartínAna M Alvarez-MéndezLaura SanzLuis Alvarez-VallinaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72957 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo Fernández-Periáñez Irene Molina-Privado Federico Rojo Irene Guijarro-Muñoz Vanesa Alonso-Camino Sandra Zazo Marta Compte Ana Alvarez-Cienfuegos Angel M Cuesta David Sánchez-Martín Ana M Alvarez-Méndez Laura Sanz Luis Alvarez-Vallina Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
description	Metastatic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention.
format	article
author	Rodrigo Fernández-Periáñez Irene Molina-Privado Federico Rojo Irene Guijarro-Muñoz Vanesa Alonso-Camino Sandra Zazo Marta Compte Ana Alvarez-Cienfuegos Angel M Cuesta David Sánchez-Martín Ana M Alvarez-Méndez Laura Sanz Luis Alvarez-Vallina
author_facet	Rodrigo Fernández-Periáñez Irene Molina-Privado Federico Rojo Irene Guijarro-Muñoz Vanesa Alonso-Camino Sandra Zazo Marta Compte Ana Alvarez-Cienfuegos Angel M Cuesta David Sánchez-Martín Ana M Alvarez-Méndez Laura Sanz Luis Alvarez-Vallina
author_sort	Rodrigo Fernández-Periáñez
title	Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
title_short	Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
title_full	Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
title_fullStr	Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
title_full_unstemmed	Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
title_sort	basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5ee65d3045ff4059abeaf2b357359dba
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Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.

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