RT Journal Article
T1 Basement Membrane-Rich Organoids with Functional Human Blood Vessels Are Permissive Niches for Human Breast Cancer Metastasis
A1 Fernández-Periáñez Rodrigo, 
A1 Molina-Privado, Irene
A1 Rojo, Federico
A1 Guijarro-Muñoz, Irene
A1 Alonso-Camino, Vanesa
A1 Zazo, Sandra
A1 Compte, Marta
A1 Álvarez-Cienfuegos, Ana
A1 Cuesta Martínez, Ángel
A1 Sánchez-Martín, David
A1 Álvarez-Méndez, Ana M.
A1 Sanz, Laura
A1 Luis Álvarez-Vallina, 
AB 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.
PB PLOS
SN 1932-6203
YR 2013
FD 2013-08-08
LK https://hdl.handle.net/20.500.14352/115358
UL https://hdl.handle.net/20.500.14352/115358
LA eng
NO Fernández-Periáñez R, Molina-Privado I, Rojo F, Guijarro-Muñoz I, Alonso-Camino V, Zazo S, Compte M, Alvarez-Cienfuegos A, Cuesta AM, Sánchez-Martín D, Alvarez-Méndez AM, Sanz L, Alvarez-Vallina L. Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis. PLoS One. 2013 Aug 8;8(8):e72957. doi: 10.1371/journal.pone.0072957. PMID: 23951338; PMCID: PMC3738545.
NO t PS09/00227 from the Fondo de Investigación Sanitaria to L.S; by grants PS09/01296, RD09/0076/00101 and RD06/0020/0109 from the Fondo de Investigación Sanitaria to FR and by grant AP86442011 from Fundación Mutua Madrileña to FR. RFP was supported by a predoctoral fellowship from the Ministerio de Economía y Competitividad (BES-2009- 027649), VAC by a predoctoral fellowship from the Gobierno Vasco (BFI07.132), PSV by a predoctoral fellowship from the Fundación Investigación Biomedica Hospital Universitario Puerta de Hierro, and DSM by a Comunidad de Madrid/Fondo Social Europeo Training Grant (FPI-000531). The funders had no role in study design, data collection and analysis, decision to publish, or p
NO Ministerio de Economía y Competitividad  (España)
NO Ministerio de Ciencia e Innovación (España)
NO Comunidad de Madrid
NO European Commission
DS Docta Complutense
RD 24 abr 2025