TY  - JOUR
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, Ángel M.
A1  - Sánchez-Martín, David
A1  - Álvarez-Méndez, Ana M.
A1  - Sanz, Laura
A1  - Álvarez-Vallina, Luis
T1  - Basement membrane-rich Organoids with functional human blood vessels are permissive niches for human breast cancer metastasis
T2  - PLoS One
N2  - Metastasic 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/31438
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-314388
SN  - 1932-6203
N1  - Copyright: © 2013 Fernández-Periañez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 8
IS  - (8):e72957
SP  - 1
EP  - 14
PB  - PLoS
CY  - Lawrence, Kan.
ER  -