Abstract
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.
Highlights
Osteosarcoma is a rare but the most frequent primary malignant bone tumor with a peak incidence in adolescence and young adulthood [1]
The main prognostic factors of relapse are the metastatic status at diagnosis and the histological response to neoadjuvant chemotherapy [5, 6]
The major difficulty in using these preclinical orthotopic bone models is the measurement of the disease burden in a nonaccessible site, which requires the use of noninvasive techniques such as radiography [16], computed tomography (CT), magnetic resonance imaging (MRI), or bioluminescence [13, 14]
Summary
Osteosarcoma is a rare but the most frequent primary malignant bone tumor with a peak incidence in adolescence and young adulthood [1]. Due to the complex osteosarcoma genetic background and the importance of bone and immune microenvironment in this tumor type [8–10], multiple osteosarcoma models representative of the human disease in different in vitro and in vivo contexts are needed to get more insight into different processes involving osteosarcoma initiation, progression especially metastatic and treatment sensitivity. Covering a large panel of osteosarcoma genetic abnormalities, these mice models might not be fully clinically relevant because osteosarcoma cells are not spontaneously arisen and do not grow in the proper site. It can be hypothesized that in vivo models in an orthotopic setting might reveal different tumor behavior: primary tumor growth, metastatic potential, and response to treatment [13–15], by better mimicking the initial bone site of the disease in patients. The major difficulty in using these preclinical orthotopic bone models is the measurement of the disease burden in a nonaccessible site, which requires the use of noninvasive techniques such as radiography [16], computed tomography (CT), magnetic resonance imaging (MRI), or bioluminescence [13, 14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
