Jaw osteosarcoma models in mice: first description

Hélios Bertin,Régis Brion,Anne Brouchet-Gomez,Benoit Piot,Dominique Heymann,Romain Guilho,Jérôme Amiaud,Anne Moreau,Françoise Rédini,Séverine Battaglia,Julie Longis,Pierre Corre

doi:10.1186/s12967-019-1807-5

Abstract

BackgroundOsteosarcoma (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.MethodsSyngenic 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.ResultsHomogeneous tumor growth was observed in both the HOS1544 and the MOS-J JOS models by injection of 0.25 × 106 and 0.50 × 106 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.ConclusionWe 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.

Highlights

Osteosarcoma (OS) is the most common cancer of bone
Development of preclinical models of mouse Jaw osteosarcoma (JOS) All of the mice injected with murine osteosarcoma cells developed a mandibular tumor
They are induced by different approaches; radiation- and chemically induced mouse models refer to DNA damage studies [2, 13], while genetically engineered mouse (GEM) models have been induced by deletion of p53 and Rb in the osteoblast lineage [23, 26], as well as by overexpression of oncogenes in osteoblastic precursors [27]

Summary

Introduction

Jaw osteosarcoma (JOS) is rare and it differs from other OS in terms of the time of occurrence (two decades later) and better survival. Jaw osteosarcoma (JOS) is a rare condition, representing only 5 to 10 percent of all osteosarcomas [3,4,5]. It differs from long-bone osteosarcomas (LBOS) as it typically occurs two decades later [5, 6], has a lower metastatic potential [4], and has better patient survival rates [6, 7]. The surgical procedure remains complicated with facial locations because it is difficult to obtain free surgical margins, leading to functional and aesthetic impairments. There is, a need for appropriate animal models that recapitulate the complexity and the heterogeneity of this malignancy [12]

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