A New Experimental Rat Model of Osteosarcoma Established by Intrafemoral Tumor Cell Inoculation, Useful for Biology and Therapy Investigations

Abstract

Satisfactory experimental models for preclinical cancer studies must follow several criteria: (1) reproducibility of the method used to induce the tumor and (2) clinical, pathological and kinetic similarity with the corresponding human tumors. We developed a model of osteosarcoma locally induced by the intrafemoral injection of osteosarcoma (OSR) cells in Sprague-Dawley rats. This method yields nearly 80% of bone tumors at the injection site. These tumors double their volume fairly slowly (in approximately 20 days) and lung metastases occur in 96% of the animals. The OSR cell-induced tumor is characterized by a direct production of mineralized matrix by the tumor cells themselves, as revealed by histochemical analysis. The microarchitectural parameters which were quantified by a microscanner show an increased trabecular bone volume (+238%) when OSR cells were injected in the femur, as compared to controls injected with vehicle. Osteoblastic markers such as alkaline phosphatase, osteopontin, osteocalcin and bone sialoprotein were expressed by the tumor in vivo, whereas the initially injected OSR cells did not express some of these markers, suggesting that OSR cells reacquired an osteoblastic phenotype in a favorable environment. The clinical, radiological and histological data show that this model shares high similarities with the osteocondensing forms of osteosarcoma in humans.

Advantages of bioluminescence imaging to follow siRNA or chemotherapeutic treatments in osteosarcoma preclinical models

“…The necrotic, fibrotic areas are included in the measurement of tumor volume, but have a lower luciferase activity than healthy, non-necrotic tumor areas. Finally, the extensive bone remodeling that is normally associated with OSRGA osteosarcoma 25 was similarly observed with LucF-OSRGA tumors. Radiography and microscanner analyses showed characteristic osteolytic lesions and ectopic bone formation along the cortical bone at the tumor implantation site (Figures 2e and f).…”

“…[22][23][24] This is the purpose of this study. Osteosarcoma models that have been established in our laboratory, 13,25 were modified to stably express the firefly luciferase using lentiviral gene transfer, then the luciferase expression was targeted with siRNA combined with the cationic liposome RPR209120 2-{3-[Bis-(3-amino-propyl)-amino]-propylamino}-N-ditetradecyl carbamoyl methyl-acetamide and DOPE (dioleyl phosphatidyl ethanolamine; Avanti Polar Lipids) 26,27 to determine the optimal delivery method for siRNA in osteosarcoma models.…”

An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma

“…Moreover, reaming the intramedullary space of the tibia is not done, likely due to the curved anatomical feature of this bone. Although the intrafemoral injection method also showed successful tumor establishment in the femur [9, 10], no publication described details of the procedures to minimize the leakage. Leakage from the bone marrow cavity could alter the onset of tumor formation and result in experimental variation or inconsistency.…”

A rabbit bone tumor model for high-intensity focused ultrasound therapy

“…The five-year survival rates were not more than 30% after the discovery of pulmonary metastasis (1). Because surgery involves too many complications and wounds and because whether or not to have another clinical surgery on partial palindromia after the operation is still disputed, treatment of malignant bone tumor has advanced from sole amputation surgery before the 1970s to complex therapy based on chemotherapy for preserving the extremity (2).…”