abstract
Transcription
abstract
EFFECT OF BONE MICROENVIRONMENT IN JAW OSTEOSARCOMA DEVELOPMENT Abstract ID : 1158 Submitted by : Françoise Redini the 2016-02-08 17:15:49 Category : Others Typology : Communication orale / Oral communication Status : Validated Authorisation to disclose : Yes/Oui ------------------------------------Background: Osteosarcoma is the most frequent malignant bone tumor in children and adolescents. Jaw osteosarcoma (JOs) differs from the long bones osteosarcoma (LBOs) in an onset two decades later and a lower metastatic potential with better survival. The treatment of the JOs remains complicated because of the aesthetic and functional disabilities due to the surgery. The aim of our work is to develop for the first time a preclinical model of JOs in order (i) to investigate the potential role played by the bone microenvironment in the JOs development, and (ii) to understand a different clinical behavior as compared with LBOs. Materials and methods: Using syngenic and xenogenic models from mouse and human osteosarcoma cell lines, and a tumor xenograft induced by patient derived JOs biopsy, we developed jaw osteosarcoma models in mice. The jaw model was compared to the tibia induced osteosarcoma model and characterized according to clinical parameters (tumor growth, metastasis dissemination), microCT imaging and histologic settings. A comparative analysis of bone markers at transcriptomic and immunohistochemical levels was carried out between the two locations. The protein expression in bone microenvironment was comparatively studied in human biopsies from jaw and long bones osteosarcomas by using tissue micro-array (TMA). Zoledronic acid targeted therapy was realized in jaw osteosarcoma model looking for a possible effect on the tumor growth and the metastatic development. Results: The tumor growth was higher in the tibia induced osteosarcoma site than in the jaw site mostly in the xenogenic model. Lung metastases were found in both models without correlation with the tumor volume. The morphometric characterization by microCT showed mixed osteogenic and osteolytic lesions as described in human disease and no histologic difference was found regardless of the model studied. Immunohistochemical, transcriptomic and TMA comparative studies are still in progress. Zoledronic acid was shown to be an effective therapy to reduce the tumor growth in mice jaw osteosarcoma. Conclusion: We describe the first animal model of jaw osteosarcoma in non-GM mice and its potential use in specific therapeutic targeting. ------------------------------------Keywords : osteosarcoma, microenvironment, bone resorption, angiogenesis Authors : References : , , , Authors Françoise REDINI 1, Hélios BERTIN 1, Romain GUIHO 1, Malika GANTIER 1, Jérôme AMIAUD 4, Julie LONGIS 5, Benoit PIOT 5, Pierre CORRE 5, Anne BROUCHET-GOMEZ 6, Dominique HEYMANN 1, 1. faculté de médecine, INSERM UMR957, Nantes, FRANCE 2. Faculté de Médecine, INSERM UMR957, Nantes, FRANCE 3. Faculté de médecine, INSERM UMR957, Nantes, FRANCE 4. Faulté de médecine, INSERM UMR957, Nantes, FRANCE 5. stomatology, CHU Hôtel Dieu, Nantes, FRANCE 6. Pathology-CRB, Oncopôle, Toulouse, FRANCE Authors (raw format) REDINI Françoise - email : [email protected] Institution : INSERM UMR957 Department : faculté de médecine City : Nantes Country : FRANCE Speaker : Yes BERTIN Hélios - email : [email protected] Institution : INSERM UMR957 Department : Faculté de Médecine City : Nantes Country : FRANCE Speaker : No GUIHO Romain - email : [email protected] Institution : INSERM UMR957 Department : Faculté de médecine City : Nantes Country : FRANCE Speaker : No GANTIER Malika - email : [email protected] Institution : INSERM UMR957 Department : Faculté de médecine City : Nantes Country : FRANCE Speaker : No AMIAUD Jérôme - email : [email protected] Institution : INSERM UMR957 Department : Faulté de médecine City : Nantes Country : FRANCE Speaker : No LONGIS Julie - email : [email protected] Institution : CHU Hôtel Dieu Department : stomatology City : Nantes Country : FRANCE Speaker : No PIOT Benoit - email : [email protected] Institution : CHU Hôtel Dieu Department : stomatology City : Nantes Country : FRANCE Speaker : No CORRE Pierre - email : [email protected] Institution : CHU Hôtel Dieu Department : stomatology City : Nantes Country : FRANCE Speaker : No BROUCHET-GOMEZ Anne - email : [email protected] Institution : Oncopôle Department : Pathology-CRB City : Toulouse Country : FRANCE Speaker : No HEYMANN Dominique - email : [email protected] Institution : INSERM UMR957 Department : Faculté de médecine City : Nantes Country : FRANCE Speaker : No