title: Murine models of breast cancer bone metastasis.
abstract: Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations forin vivoandex vivoassessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone.
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University , Indianapolis, IN, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Wright
authors.affiliation: Department of Oncology, Mellanby Center for Bone Research, University of Sheffield , Sheffield, UK.
authors.forename: Penelope D
authors.initials: PD
authors.lastname: Ottewell
authors.affiliation: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila , L'Aquila, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rucci
authors.affiliation: Physiopathologie, Diagnostic et Traitements des Maladies Osseuses, INSERM, UMR_S1033 , Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Peyruchaud
authors.affiliation: Department of Biomedical Engineering, Stony Brook University , Stony Brook, NY, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Pagnotti
authors.affiliation: Division of Endocrinology, Department of Medicine, Indiana University , Indianapolis, IN, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Chiechi
authors.affiliation: Department of Thrombosis & Hemostasis, Leiden University Medical Center , Leiden, The Netherlands.
authors.forename: Jeroen T
authors.initials: JT
authors.lastname: Buijs
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sterling