title: Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model.
abstract: 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.
authors.affiliation: 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. laura.mercatali@irst.emr.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
authors.affiliation: 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. federico.lamanna@gmail.com.|Department of Urology, Leiden University Medical Center, J-3-100, Albinusdreef 2, 2333ZA Leiden, The Netherlands. federico.lamanna@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: La Manna
authors.affiliation: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE Leiden, The Netherlands. a.groenewoud@biology.leidenuniv.nl.
authors.forename: Arwin
authors.initials: A
authors.lastname: Groenewoud
authors.affiliation: Department of Orthopedics, Istituto Ortopedico Rizzoli, University of Bologna, Via Pupilli, 1, 40136 Bologna, Italy. roberto.casadei@ior.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Casadei
authors.affiliation: 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. federica.recine@irst.emr.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Recine
authors.affiliation: 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. giacomo.miserocchi@irst.emr.it.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Miserocchi
authors.affiliation: Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy. federica.pieri@auslromagna.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Pieri
authors.affiliation: 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. chiara.liverani@irst.emr.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Liverani
authors.affiliation: 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. alberto.bongiovanni@irst.emr.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: 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. chiara.spadazzi@irst.emr.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Spadazzi
authors.affiliation: 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. alessandro.devita@irst.emr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: de Vita
authors.affiliation: Department of Urology, Leiden University Medical Center, J-3-100, Albinusdreef 2, 2333ZA Leiden, The Netherlands. g.van.der.pluijm@umail.leidenuniv.nl.
authors.forename: Gabri
authors.initials: G
authors.lastname: van der Pluijm
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, Modena Polyclinic, Viale del Pozzo, 71, 41124 Modena, Italy. andreagiorgini@hotmail.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giorgini
authors.affiliation: UOC Orthopedic Surgery, Regina Elena National Cancer Institute, 00144 Rome, Italy. biagini@ifo.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Biagini
authors.affiliation: 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. dino.amadori@irst.emr.it.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: 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. toni.ibrahim@irst.emr.it.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE Leiden, The Netherlands. b.e.snaar-jagalska@biology.leidenuniv.nl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Snaar-Jagalska
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
keywords: bone metastasis; breast cancer; patient-derived xenograft; zebrafish model