Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice
Autor: | Massimo Serra, Katia Scotlandi, Estelle Daudigeos-Dubus, Anne Gomez-Brouchet, Valérie Rouffiac, Maria Eugenia Marques da Costa, Olivia Bawa, Conceição Santos, Birgit Geoerger, Nathalie Gaspar |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research Mice Nude Context (language use) 03 medical and health sciences Mice 0302 clinical medicine Immune system In vivo Cell Line Tumor medicine Animals Humans Radiology Nuclear Medicine and imaging Original Research Osteosarcoma business.industry human osteosarcoma Clinical Cancer Research cell‐derived xenograft medicine.disease Primary tumor Xenograft Model Antitumor Assays in vivo orthotopic Disease Models Animal 030104 developmental biology Primary bone Oncology Tumor progression 030220 oncology & carcinogenesis Luminescent Measurements Cancer research NSG mouse Bioluminescence business |
Zdroj: | Cancer Medicine |
ISSN: | 2045-7634 |
Popis: | Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell‐derived xenograft (CDX) models, Saos‐2‐B‐Luc/mKate2‐CDX and HOS‐Luc/mKate2‐CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real‐time follow‐up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos‐2‐B‐Luc/mKate2‐CDX showed osteocondensed, HOS‐Luc/mKate2‐CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos‐2‐B‐Luc/mKate2‐CDX than in HOS‐Luc/mKate2‐CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models. |
Databáze: | OpenAIRE |
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