New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance

Monderer, David; Luseau, Alexandrine; Bellec, Amelie; David, Emmanuelle; Ponsolle, Stéphanie; Saïagh, Soraya; Bercegeay, Sylvain; Piloquet, Philippe; Denis, Marc G.; Lodé, Laurence; Rédini, Françoise; Biger, Marine; Heymann, Dominique; Heymann, Marie-Françoise; Bot, Ronan Le; Blanchard, Frédéric

doi:10.1530/boneabs.1.pp138

Cited by 6 publications

(7 citation statements)

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“…A comprehensive analysis of DDC and COS showed that both had cartilage components. Monderer et al 25 found that cartilage components may have an inhibitory effect on chemotherapy. They constructed primary central chondrosarcoma cell lines from stage III tumors and DDC cell lines and designed a three-dimensional culture model to maintain their differentiation into chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the clinical outcomes and prognostic factors of dedifferentiated chondrosarcoma and chondroblastic osteosarcoma: a population-based analysis

Bian

Zeng

Yao

et al. 2020

Preprint

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Background Dedifferentiated chondrosarcoma (DDC) and chondroblastic osteosarcoma (COS) have some common morphological characteristics by pathology and involve the same surgical methods and chemotherapy regimen. We explored the prognostic differences and factors of patients with DDC and COS with similar pathological features to analyze the prognostic factors and effect of chemotherapy on the prognosis of each type. Methods From the SEER database, we included 228 patients with DDC and 631 patients with COS who underwent surgery from 1975 to 2016. Patient age was stratified with X-tile, and prognosis was analyzed by the Kaplan-Meier method and Cox proportional hazard regression. Results The 3- and 5-year overall survival (OS) rates for DDC were 33.3% and 26.5%, respectively, and the 3- and 5-year OS rates for COS were 71.5% and 63.8%, respectively. Compared with COS, DDC had an older onset age, a higher proportion of white patients, an increased likelihood of occurrence in soft tissue, a higher pathological grade, a larger tumor volume, more patients with M1-stage, a higher AJCC stage and a lower chemotherapy utilization rate. Univariate analysis showed that age, M1 stage and high tumor stage were negatively correlated with DDC patient prognosis, with a worse prognosis for patients with lung metastasis. In the multivariate analysis, higher tumor stage was an independent factor for reducing OS in DDC. Univariate analysis showed that COS patients were older and male; had tumors located in the pelvis; had high T-, M-, and AJCC-stage tumors; and had lung metastasis. Moreover, no chemotherapy was negatively correlated with patient prognosis. Furthermore, age, male sex and high tumor stage were independent factors for reducing OS in COS. Conclusion The OS of DDC patients is worse than that of COS patients. Chemotherapy cannot benefit patients with DDC. For COS patients, further exploration of the survival benefits of chemotherapy is needed.

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Section: Discussionmentioning

confidence: 99%

Comparison of the clinical outcomes and prognostic factors of dedifferentiated chondrosarcoma and chondroblastic osteosarcoma: a population-based analysis

Bian

Zeng

Yao

et al. 2020

Preprint

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“…This may be associated with the low proliferation rates of the tumor cells and the difficulty in reproducing an adequate environment for CS development (9).…”

Section: Introductionmentioning

confidence: 99%

Centrosome amplification in chondrosarcomas: A primary cell culture and cryopreserved tumor sample study

Pinheiro¹,

Soares²,

Penna³

et al. 2017

Oncology Letters

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“…It is likely that conventional in vitro assays based on monolayer cultures of tumor cells are not sufficient to reproduce the three‐dimensional (3D) structure of CS . To overcome this limitation, 3D chondrogenic culture models have been set up, in which CS cells cultured in 3D produce cartilaginous matrix, thus resembling the original tissue architecture. CS cells cultured in chondrogenic 3D pellets have been reported to be resistant to doxorubicin (DXR) and mafosfamide .…”

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confidence: 99%

“…To overcome this limitation, 3D chondrogenic culture models have been set up, in which CS cells cultured in 3D produce cartilaginous matrix, thus resembling the original tissue architecture. CS cells cultured in chondrogenic 3D pellets have been reported to be resistant to doxorubicin (DXR) and mafosfamide . Such 3D‐associated chemoresistance is very likely mediated by the tumor microenvironment that is recapitulated in the 3D structure, and that is typically characterized by hypoxic and acidic areas due to cancer cells tendency to glucose consumption with increased lactate production and a consequent high proton flow .…”

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confidence: 99%

Spheroid‐based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma

Perut

Sbrana

Avnet

et al. 2018

Journal Orthopaedic Research

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Chondrosarcoma (CS) is a cartilage malignancy of adulthood that is treated by surgery alone, since chemotherapy is considered ineffective. Unfortunately, a large proportion of patients with CS develop lung metastases, and several die of the disease. In this study, we compared 3D-spheroid cultures and conventional cell monolayer models in order to identify the best way to select anticancer agents that could be effective for the systemic control of CS. Using SW1353 cells, we developed a three-dimensional (3D) in vitro culture model to mimic in vivo features of CS microenvironment and evaluated the efficacy of different drugs to modulate CS cell proliferation and survival in 2D versus 3D-cultures. Doxorubicin (DXR) and cisplatin, that are widely employed in sarcomas, were less effective on 3D-CS spheroids when compared to standard monolayer models, whereas treatment with the ionophore salinomycin (SAL) had a strong cytotoxic effect both on 2D and 3D-cultures. Furthermore, as demonstrated by the reduced viability and the enhanced DXR nuclear localization, SAL enhanced DXR cytotoxicity in 3D-CS spheroids also at sub-lethal doses. SAL activity on 3D-CS spheroids was mediated by a significant induction of apoptosis via caspase activation. This study demonstrates that preclinical tests significantly differ in monolayer and 3D cultures of CS cells. Using this approach, SAL, alone or, at sub-lethal concentrations, in combination with DXR, represents a promising agent for the systemic treatment of CS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance

Cited by 6 publications

References 0 publications

Comparison of the clinical outcomes and prognostic factors of dedifferentiated chondrosarcoma and chondroblastic osteosarcoma: a population-based analysis

Comparison of the clinical outcomes and prognostic factors of dedifferentiated chondrosarcoma and chondroblastic osteosarcoma: a population-based analysis

Centrosome amplification in chondrosarcomas: A primary cell culture and cryopreserved tumor sample study

Spheroid‐based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma

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