title: Biological characterization of preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model: A multi-modality approach.
abstract: Osteosarcoma (OS) is a bone malignancy that affects children and adolescents. It is a highly aggressive tumor and typically metastasizes to lungs. Despite aggressive chemotherapy and surgical treatments, the current 5 year survival rate is 60-70%. Clinically relevant models are needed to understand OS pathobiology, metastatic progression from bones to lungs, and ultimately, to develop more efficacious treatment strategies and improve survival rates in OS patients with metastasis. The main goal of this study was to develop and characterize anin vivoOS model that will allow non-invasive tracking of tumor progression in real time, and aid in studying OS pathobiology, and screening of potential therapeutic agents against OS. In this study, we have used a multi-modality approach using bioluminescent imaging, electron microscopy, micro-computed tomography, and histopathology to develop and characterize a preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model, using 143B human OS cell line. The results of this study clearly demonstrate that the BOOM model represents the clinical disease as evidenced by a spectrum of changes associated with tumor establishment, progression and metastasis, and detection of known OS biomarkers in the primary and metastatic tumor tissue. Key novel findings of this study include: (a) multimodality approach for extensive characterization of the BOOM model using 143B human OS cell line; (b) evidence of renal metastasis in OS orthotopic model using 143B cells; (c) evidence of Runx2 expression in the metastatic lung tissue; and (d) evidence of the presence of extracellular membrane vesicles and myofibroblasts in the BOOM model.
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA ; Division of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS, USA ; Division of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Rama
authors: R
authors: Garimella
authors: The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Jeff
authors: J
authors: Eskew
authors: Division of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Priyanka
authors: P
authors: Bhamidi
authors: The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA ; Division of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
authors: George
authors: G
authors: Vielhauer
authors: Division of Gynecology and Obstetrics, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Yan
authors: Y
authors: Hong
authors: Division of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors: H Clarke
authors: HC
authors: Anderson
authors: Division of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Ossama
authors: O
authors: Tawfik
authors: Division of Nephrology, Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA.
authors: Peter
authors: P
authors: Rowe
keywords: Bioluminescent; Extra-cellular membrane vesicles; Myofibroblasts; Orthotopic; Osteosarcoma; Preclinical