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Int. J. Mol. Sci. 2016, 17(8), 1375;

Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model

Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy
Department of Urology, Leiden University Medical Center, J-3-100, Albinusdreef 2, 2333ZA Leiden, The Netherlands
Department of Molecular Cell Biology, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE Leiden, The Netherlands
Department of Orthopedics, Istituto Ortopedico Rizzoli, University of Bologna, Via Pupilli, 1, 40136 Bologna, Italy
Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy
Department of Medical and Surgical Sciences for Children and Adults, Modena Polyclinic, Viale del Pozzo, 71, 41124 Modena, Italy
UOC Orthopedic Surgery, Regina Elena National Cancer Institute, 00144 Rome, Italy
Author to whom correspondence should be addressed.
Academic Editors: Maria Alfonsina Desiderio and Dario Marchetti
Received: 27 June 2016 / Revised: 4 August 2016 / Accepted: 16 August 2016 / Published: 22 August 2016
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Bone Metastasis)
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Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient’s medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model. View Full-Text
Keywords: bone metastasis; zebrafish model; breast cancer; patient-derived xenograft bone metastasis; zebrafish model; breast cancer; patient-derived xenograft

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Mercatali, L.; La Manna, F.; Groenewoud, A.; Casadei, R.; Recine, F.; Miserocchi, G.; Pieri, F.; Liverani, C.; Bongiovanni, A.; Spadazzi, C.; de Vita, A.; van der Pluijm, G.; Giorgini, A.; Biagini, R.; Amadori, D.; Ibrahim, T.; Snaar-Jagalska, E. Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model. Int. J. Mol. Sci. 2016, 17, 1375.

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