Biological characterization of preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model: A multi-modality approach
Rama Garimella,Jeff Eskew,Priyanka Bhamidi,George A. Vielhauer,Yan Hong,H. Clarke Anderson,Ossama Tawfik,Peter S. N. Rowe +7 more
TLDR
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.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 an in vivo OS 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.read more
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Extracellular Membrane Vesicles Derived from 143B Osteosarcoma Cells Contain Pro-Osteoclastogenic Cargo: A Novel Communication Mechanism in Osteosarcoma Bone Microenvironment.
Rama Garimella,Laurie Washington,Janalee Isaacson,Julian Vallejo,Madoka Spence,Ossama Tawfik,Peter S. N. Rowe,Marco Brotto,Raymond P. Perez +8 more
TL;DR: It is demonstrated that 143B osteosarcoma cells generate EMVs mainly by mechanisms involving increased intracellular calcium or cAMP levels, and contain pro-osteoclastic cargo.
Journal ArticleDOI
Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and Is Not a Spontaneous Model of Metastasis: A Mouse Osteosarcoma Model.
Caroline Maloney,Morris Edelman,Michelle P. Kallis,Samuel Z. Soffer,Marc Symons,Bettie M. Steinberg +5 more
TL;DR: A widely used murine model of metastatic osteosarcoma is characterized and whether it is appropriate to study spontaneous pulmonary metastasis by establishing a reliable volume for intratibial injection and the kinetics of pulmonary metastatic seeding and outgrowth are determined.
Journal ArticleDOI
Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.
Milcah C. Scott,Hirotaka Tomiyasu,John R. Garbe,Ingrid Cornax,Clarissa N. Amaya,M. Gerard O'Sullivan,Subbaya Subramanian,Brad A. Bryan,Jaime F. Modiano +8 more
TL;DR: Cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior are used for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of bone cancer in mouse models and novel methods to study tumor–stromal interactions in these models are described.
Journal ArticleDOI
Extracellular vesicles-mediated signaling in the osteosarcoma microenvironment: Roles and potential therapeutic targets
TL;DR: The roles of EVs in the physiology and pathogenesis of OS and the potential attractive therapeutic target for the treatment of OS were reviewed.
Journal ArticleDOI
Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells
Rama Garimella,Priyanka Tadikonda,Ossama Tawfik,Sumedha Gunewardena,Peter S. N. Rowe,Peter J. Van Veldhuizen +5 more
TL;DR: Vitamin D inhibited the expression of Runx2 target genes MMP1, MMP28 and kallikrein related peptidase-7 (KLK7), but also migration and invasion of 143B OS cells.
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