Jaw osteosarcoma models in mice: first description

Abstract

Background Osteosarcoma (OS) is the most common cancer of bone. Jaw osteosarcoma (JOS) is rare and it differs from other OS in terms of the time of occurrence (two decades later) and better survival. The aim of our work was to develop and characterize specific mouse models of JOS. Methods Syngenic and xenogenic models of JOS were developed in mice using mouse (MOS-J) and human (HOS1544) osteosarcoma cell lines, respectively. An orthotopic patient-derived xenograft model (PDX) was also developed from a mandibular biopsy. These models were characterized at the histological and micro-CT imaging levels, as well as in terms of tumor growth and metastatic spread. Results Homogeneous tumor growth was observed in both the HOS1544 and the MOS-J JOS models by injection of 0.25 × 10 6 and 0.50 × 10 6 tumor cells, respectively, at perimandibular sites. Histological characterization of the tumors revealed features consistent with high grade conventional osteosarcoma, and the micro-CT analysis revealed both osteogenic and osteolytic lesions. Early metastasis was encountered at day 14 in the xenogenic model, while there were no metastatic lesions in the syngenic model and in the PDX models. Conclusion We describe the first animal model of JOS and its potential use for therapeutic applications. This model needs to be compared with the usual long-bone osteosarcoma models to investigate potential differences in the bone microenvironment. Electronic supplementary material The online version of this article (10.1186/s12967-019-1807-5) contains supplementary material, which is available to authorized users.

Imaging Hallmarks of Sarcoma Progression Via X-ray Computed Tomography: Beholding the Flower of Evil

“…Computed X-ray micro-tomography (micro-CT) is an imaging technique enabling 3D non-destructive tissue visualization with a minimum voxel size of 1–5 μm 3 [ 94 ], providing an opportunity to study tumors in their native state as well as their original spatial interactions with the microenvironment [ 95 ]. Using micro-CT, we can visualize key changes in bone microarchitecture associated with tumor development in live animals and, moreover, compare them among different osteosarcoma models and quantify these changes via bone volume, and cortical and trabecular bone measurements, such as trabecular number and trabecular thickness [ 84 , 85 , 96 , 97 , 98 ]. We can also study the early stages of tumor growth before there is a palpable tumor mass, determine the type of bone lesion (osteoblastic or osteolytic), and the animal’s apparent metastatic sites [ 81 ].…”

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“…Data show that the survival rate of patients with osteosarcoma has not changed over the last 40 years; therefore, there is an imminent need for more effective therapeutic approaches. 21,22…”

Osteoimmunology of Oral and Maxillofacial Diseases: Translational Applications Based on Biological Mechanisms

“…MFOS represent <10% of the total OS (165). Compared with the appendicular OS, which peaks in the 2nd and sixth decade, MFOS peaks in the 3rd decade (162, 163, 165). Typically, MFOS arise from the cancellous compartment rather than bony surfaces.…”

“…MFOS affects the alveolar ridge of the mandible and posterior area of the maxilla (163, 166). MFOS can be categorized according to the predominant matrix as an osteoblastic, fibroblastic, chondroblastic, telangiectatic, or osteoclastic type (163, 165). At the X-ray imaging, MFOS appear as either as the osteolytic form with undefined margins or, the osteoblastic form, showing a sclerotic and sunburst structure caused by radiated bone spiculae (163).…”