Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical relevance and applicability for drug testing

Dass, Crispin R.; Ek, Eugene T.; Choong, Peter F. M.

doi:10.1007/s00432-006-0157-x

Cited by 35 publications

(30 citation statements)

References 37 publications

(34 reference statements)

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“…This indicates metastatic potential and excludes that the lung metastases are a result of migrating cells after injection of a loose cell mass into the mice. The availability of HOS-143B non-tumorigenic parental cell line HOS and its tumorigenic, but nonmetastatic progeny cell line HOS-MNNG, 38 makes these three cell lines excellent models to comparatively study osteosarcoma progression and metastasis, respectively. For example, the TP53 mutation found in all three cell lines might suggest that p53 has a role in tumor initiation, but not that much in progression and metastasis, and that additional events (HOS-MNNG was generated by the chemical agent Nmethyl-N 0 -nitro-N-nitroguanidineare and HOS-134B via a Ki-ras oncogene transformation) are needed.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

Mohseny

Machado

Cai

et al. 2011

Laboratory Investigation

164

151

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Cancer cell lines represent in vitro models for studying malignancies, general cell biology, drug discovery and more. Whether they can be considered as exact representative models of the parental tumors remains uncertain given the acquisition of additional ex vivo changes of the cells and the lack of tissue architecture and stroma. Previously, within the EuroBoNeT consortium, we characterized a collection of bone sarcoma cell lines on genomic and proteomic level. Here, we address the phenotypical and functional characterization of the unique set of osteosarcoma cell lines (n ¼ 19) in vitro and in vivo. For functional analysis of differentiation capacity, cells were stimulated towards osteoblasts, adipocytes and chondrocytes. Furthermore, all cell lines were injected subcutaneously and intramuscularly into nude mice to assay their in vivo tumor formation capacity as well as for phenotypical analysis of the tumors. All formed tumors were further characterized histologically and immunohistochemically. Out of 19 cell lines, 17 (89%) showed adipogenic differentiation, 13/19 (68%) could differentiate towards osteoblasts and in 6/19 (32%) cell lines chondrogenic differentiation was evident. About half of the cell lines (8/19, 42%) produced tumors in vivo after subcutaneous and intramuscular injections. Several cell lines showed invasion into adjacent tissues and one tumor developed several lung metastases. The use of cell lines, especially in cancer research, is of paramount importance. Here, we identify comprehensively characterized osteosarcoma cell lines, which robustly represent clinical osteosarcoma providing researchers useful in vitro and in vivo models to study the genetics and functional characteristics of this highly malignant neoplasm.

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Section: Discussionmentioning

confidence: 99%

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

Mohseny

Machado

Cai

et al. 2011

Laboratory Investigation

164

151

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“…There have been numerous murine tumor models of OS developed recently [4][5][6][7][8][9][10][11][12][13][14][15][16]. These models include xenogeneic [4, 6-9, 13, 15] and syngeneic [10,11,14,17] murine tumor models that have been used to better understand the biology of OS.…”

Section: Introductionmentioning

confidence: 99%

An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis

Sottnik

Duval

Ehrhart

et al. 2010

Clin Exp Metastasis

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Osteosarcoma (OS) is the most common bone tumor in humans. Newer, more clinically relevant models of OS are required to investigate novel therapeutics. The ability to study spontaneous micrometastases in the absence of a primary tumor is important since this is the manner in which most patients are treated clinically. Therefore, we have developed a novel model of murine OS using the DLM8 cell line, which is syngeneic to C3H mice. We have engineered these cells to express firefly luciferase so the development of metastases can be followed serially and non-invasively. These cells form osteolytic/osteoproductive lesions and metastasize spontaneously after orthotopic implantation in the proximal tibia, and the development of soft-tissue metastasis can be followed serially by luciferase expression following amputation. We have demonstrated a significant prolongation of disease-free and overall survival in the surgical adjuvant setting following treatment with doxorubicin or carboplatin, drugs which form the mainstay of treatment for human OS. In conclusion, we have developed a novel surgical adjuvant model of metastatic OS in immunocompetent mice that closely recapitulates the clinical situation, allowing the evaluation of novel therapeutics in the context of minimal residual disease.

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“…The injected cells form a solid tumor locally grown within days or weeks after implantation (42, 43). The use of these systems has become a prominent tool in current oncological research due to the quick onset, its affordable cost, and ease of handling and maintenance.…”

Section: Xenotransplantation Studiesmentioning

confidence: 99%

Animal Models in Osteosarcoma

2014

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Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Toward a better understanding of the molecular pathogenesis of human OS, several genetically modified OS mouse models have been developed and will be reviewed here. However, better animal models that more accurately recapitulate the natural progression of the disease are needed for the development of improved prognostic and diagnostic markers as well as targeted therapies for both primary and metastatic OS.

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Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical relevance and applicability for drug testing

Cited by 35 publications

References 37 publications

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

Functional characterization of osteosarcoma cell lines provides representative models to study the human disease

An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis

Animal Models in Osteosarcoma

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