Non-rodent animal models of osteosarcoma: A review

Jarvis, Sommer; Koumadoraki, Evgenia; Madouros, Nikolaos; Sharif, Shayka; Saleem, Amber; Khan, Safeera

doi:10.1016/j.ctarc.2021.100307

Cited by 11 publications

(7 citation statements)

References 63 publications

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“…Different disease stages of human colorectal cancer from low-grade to high-grade polyps as well as human osteosarcomas can be mimicked by genetic engineering. Porcine osteosarcoma models helped to elucidate novel pathways to study this tumor entity on a molecular level (Sieren et al 2014 ; Saalfrank et al 2016 ; Tanihara et al 2018 ; Jarvis et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Salvermoser

Flisikowski

Dressel

et al. 2023

Cell Stress and Chaperones

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Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC1311/+ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53R167H pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals.

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Section: Introductionmentioning

confidence: 99%

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Salvermoser

Flisikowski

Dressel

et al. 2023

Cell Stress and Chaperones

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“…Herein we innovatively propose to develop copper (Cu) and manganese (Mn) doped borosilicate nanoparticles (BSNs) to address the issue, and the resulting Cu/Mn-doped BSNs can achieve not only enhanced osteogenesis and angiogenesis for bone regeneration, but also the ability of killing tumor cells due to hydroxyl radicals produced by Fenton-like reactions of Cu 2+ and Mn 3+ . In this study, we tried to build up two types of animal model to respectively evaluate the effects, since an actual bone osteosarcoma implantation model is technically challenging [ 45 ], for example, the number of residual tumor cells after osteosarcoma resection cannot be kept consistent between animals, which will have a huge impact on the experimental results. Moreover, due to the uncontrollable number of residual tumor cells, it is difficult to evaluate the anti-tumor performance of BSNs through observation of a few animals.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment

Pang

Zhao

Chen

et al. 2022

Bioactive Materials

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Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical challenge. The present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor cells. Herein, Cu and Mn-doped borosilicate nanoparticles (BSNs) were developed for syncretic bone repairing and anti-tumor treatment, which can enhance bone regeneration through the osteogenic effects of Cu 2+ and Mn 3+ ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu 2+ and Mn 3+ ions. In vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs, and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo evaluation. Meanwhile, BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment, promote the generation of intracellular reactive oxygen species, and eventually induce tumor cell apoptosis. Besides, subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and organs. Altogether, Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration, and inhibiting tumor growth for chemodynamic therapy, thus holding a great potential for syncretic bone repairing and anti-tumor therapy.

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“…Dogs have been described as excellent models of human osteosarcoma given the striking similarities in presentation of the disease in canines and humans, including risk factors, location, disease etiology and metastatic profile [ 22 , 23 ]. Expression levels of markers associated with human OSA including alkaline phosphatase, desmin, bone morphogenetic protein 4 and runt related transcription factor 2 were described in spontaneously arising canine osteosarcoma [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of Sex Hormone Receptors in Canine Osteosarcoma

Dilley

Wong

Kent

et al. 2022

Veterinary Sciences

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Sex steroids regulate bone metabolism directly and indirectly through receptors on bone. Estrogen receptors (ER-∝, ER-β), progesterone receptor (PR), and androgen receptor (AR), have been previously identified on human osteosarcoma (OSA) cells, and are considered to influence tumor growth, but their expression and role in canine OSA is unknown. The aim of this study was to characterize sex hormone receptor expression levels in naturally occurring OSA tissue and in three canine OSA cell lines. The expression of ER-α, ER-β, PR, and AR was investigated using RT-PCR. PR expression levels were also quantified in OSA cells cultured under hypoxic conditions or in the presence of estradiol. The effects of progesterone on cell proliferation were quantified. Results demonstrated varying expression levels of these receptors in five OSA subtypes. OSA cell lines demonstrated high gene expression levels of PR and low gene expression levels of ER-α and ER-β and no gene expression of AR. PR expression was increased in OSA cells cultured under hypoxic conditions in a HIF-∝ independent manner. Interestingly, one cell line expressed very high levels of PR, expression of which decreased in response to estradiol. In addition, progesterone decreased OSA cell proliferation in this particular cell line. Further investigation of the role of sex steroids, particularly PR and its ligands, in regulation of canine OSA is recommended.

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Non-rodent animal models of osteosarcoma: A review

Cited by 11 publications

References 63 publications

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment

Expression of Sex Hormone Receptors in Canine Osteosarcoma

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