Camille JUBELIN
Doctorante Université
janvier 2020 - juin 2023
| Équipe : |
Thèmes de recherche
Développement de modèles tri-dimensionnels de cultures cellulaire in vitro pour l’étude de la progression tumorale et le screening de drogues.
Publications
1 publication
Jubelin, Camille; Muñoz-Garcia, Javier; Ollivier, Emilie; Cochonneau, Denis; Vallette, François; Heymann, Marie-Françoise; Oliver, Lisa; Heymann, Dominique
Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures Article de journal
Dans: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, p. 119660, 2024, ISSN: 0167-4889.
@article{JUBELIN2024119660,
title = {Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures},
author = {Camille Jubelin and Javier Muñoz-Garcia and Emilie Ollivier and Denis Cochonneau and François Vallette and Marie-Françoise Heymann and Lisa Oliver and Dominique Heymann},
url = {https://www.sciencedirect.com/science/article/pii/S016748892400003X},
doi = {https://doi.org/10.1016/j.bbamcr.2024.119660},
issn = {0167-4889},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular Cell Research},
pages = {119660},
abstract = {Dormancy is a potential way for tumors to develop drug resistance and escape treatment. However, the mechanisms involved in cancer dormancy remain poorly understood. This is mainly because there is no in vitro culture model making it possible to spontaneously induce dormancy. In this context, the present work proposes the use of three-dimensional (3D) spheroids developed from osteosarcoma cell lines as a relevant model for studying cancer dormancy. MNNG-HOS, SaOS-2, 143B, MG-63, U2OS and SJSA-1 cell lines were cultured in 3D using the Liquid Overlay Technique (LOT). Dormancy was studied by staining cancer cells with a lipophilic dye (DiD), and long-term DiD+ cells were considered as dormant cancer cells. The role of the extracellular matrix in inducing dormancy was investigated by embedding cells into methylcellulose or Geltrex™. Gene expression of DiD+ cells was assessed with a Nanostring™ approach and the role of the genes detected in dormancy was validated by a transient down-expression model using siRNA treatment. Proliferation was measured using fluorescence microscopy and the xCELLigence technology. We observed that MNNG-HOS, 143B and MG-G3 cell lines had a reduced proliferation rate in 3D compared to 2D. U2OS cells had an increased proliferation rate when they were cultured in Geltrex™ compared to other 3D culture methods. Using 3D cultures, a transcriptomic signature of dormancy was obtained and showed a decreased expression of 18 genes including ETV4, HELLS, ITGA6, MCM4, PRKDC, RAD21 and UBE2T. The treatment with siRNA targeting these genes showed that cancer cell proliferation was reduced when the expression of ETV4 and MCM4 were decreased, whereas proliferation was increased when the expression of RAD21 was decreased. 3D culture facilitates the maintenance of dormant cancer cells characterized by a reduced proliferation and less differential gene expression as compared to proliferative cells. Further studies of the genes involved has enabled us to envisage their role in regulating cell proliferation.},
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pubstate = {published},
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Dormancy is a potential way for tumors to develop drug resistance and escape treatment. However, the mechanisms involved in cancer dormancy remain poorly understood. This is mainly because there is no in vitro culture model making it possible to spontaneously induce dormancy. In this context, the present work proposes the use of three-dimensional (3D) spheroids developed from osteosarcoma cell lines as a relevant model for studying cancer dormancy. MNNG-HOS, SaOS-2, 143B, MG-63, U2OS and SJSA-1 cell lines were cultured in 3D using the Liquid Overlay Technique (LOT). Dormancy was studied by staining cancer cells with a lipophilic dye (DiD), and long-term DiD+ cells were considered as dormant cancer cells. The role of the extracellular matrix in inducing dormancy was investigated by embedding cells into methylcellulose or Geltrex™. Gene expression of DiD+ cells was assessed with a Nanostring™ approach and the role of the genes detected in dormancy was validated by a transient down-expression model using siRNA treatment. Proliferation was measured using fluorescence microscopy and the xCELLigence technology. We observed that MNNG-HOS, 143B and MG-G3 cell lines had a reduced proliferation rate in 3D compared to 2D. U2OS cells had an increased proliferation rate when they were cultured in Geltrex™ compared to other 3D culture methods. Using 3D cultures, a transcriptomic signature of dormancy was obtained and showed a decreased expression of 18 genes including ETV4, HELLS, ITGA6, MCM4, PRKDC, RAD21 and UBE2T. The treatment with siRNA targeting these genes showed that cancer cell proliferation was reduced when the expression of ETV4 and MCM4 were decreased, whereas proliferation was increased when the expression of RAD21 was decreased. 3D culture facilitates the maintenance of dormant cancer cells characterized by a reduced proliferation and less differential gene expression as compared to proliferative cells. Further studies of the genes involved has enabled us to envisage their role in regulating cell proliferation.
3 publications
Jubelin, Camille; Muñoz-Garcia, Javier; Griscom, Laurent; Cochonneau, Denis; Ollivier, Emilie; Heymann, Marie-Françoise; Vallette, François M; Oliver, Lisa; Heymann, Dominique
Three-dimensional in vitro culture models in oncology research Article de journal
Dans: Cell Biosci, vol. 12, no. 1, p. 155, 2022, ISSN: 2045-3701.
@article{pmid36089610,
title = {Three-dimensional in vitro culture models in oncology research},
author = {Camille Jubelin and Javier Muñoz-Garcia and Laurent Griscom and Denis Cochonneau and Emilie Ollivier and Marie-Françoise Heymann and François M Vallette and Lisa Oliver and Dominique Heymann},
doi = {10.1186/s13578-022-00887-3},
issn = {2045-3701},
year = {2022},
date = {2022-09-01},
urldate = {2022-09-01},
journal = {Cell Biosci},
volume = {12},
number = {1},
pages = {155},
abstract = {Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro. The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the constraint, and the fields of application of these models and their techniques of production are also discussed.},
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tppubtype = {article}
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Cancer is a multifactorial disease that is responsible for 10 million deaths per year. The intra- and inter-heterogeneity of malignant tumors make it difficult to develop single targeted approaches. Similarly, their diversity requires various models to investigate the mechanisms involved in cancer initiation, progression, drug resistance and recurrence. Of the in vitro cell-based models, monolayer adherent (also known as 2D culture) cell cultures have been used for the longest time. However, it appears that they are often less appropriate than the three-dimensional (3D) cell culture approach for mimicking the biological behavior of tumor cells, in particular the mechanisms leading to therapeutic escape and drug resistance. Multicellular tumor spheroids are widely used to study cancers in 3D, and can be generated by a multiplicity of techniques, such as liquid-based and scaffold-based 3D cultures, microfluidics and bioprinting. Organoids are more complex 3D models than multicellular tumor spheroids because they are generated from stem cells isolated from patients and are considered as powerful tools to reproduce the disease development in vitro. The present review provides an overview of the various 3D culture models that have been set up to study cancer development and drug response. The advantages of 3D models compared to 2D cell cultures, the constraint, and the fields of application of these models and their techniques of production are also discussed.
Jubelin, Camille; Cochonneau, Denis; Moranton, Emilie; Munoz-Garcia, Javier; Heymann, Dominique
Circulating Tumor Cells and ctDNA in Sarcomas Chapitre d'ouvrage
Dans: Leong, Stanley P.; Nathanson, S. David; Zager, Jonathan S. (Ed.): Cancer Metastasis Through the Lymphovascular System, p. 121–128, Springer, 2022.
@inbook{jubelin2022circulating,
title = {Circulating Tumor Cells and ctDNA in Sarcomas},
author = {Camille Jubelin and Denis Cochonneau and Emilie Moranton and Javier Munoz-Garcia and Dominique Heymann},
editor = {Stanley P. Leong and S. David Nathanson and Jonathan S. Zager},
doi = {10.1007/978-3-030-93084-4_12},
year = {2022},
date = {2022-06-25},
urldate = {2022-06-25},
booktitle = {Cancer Metastasis Through the Lymphovascular System},
pages = {121--128},
publisher = {Springer},
abstract = {Sarcomas are clustered in two oncological entities named bone and soft tissue sarcomas. Both are rare cancers originating from the mesenchyme, characterized by their propensity to induce the development of lung metastases. Sarcoma cells escaping from the primary tumor site spread to the pulmonary tissue through the bloodstream where they found a favorable microenvironment to establish metastatic foci. The low number of patients, the high histological, genetic, and molecular heterogeneity of sarcomas combined with the absence of specific markers expressed by cancer cells make the detection and follow-up of the minimal residual disease challenging. Over the last decade, tremendous technological progress has been made towards the detection of recurrent diseases. The literature is now enriched of information describing the use of liquid biopsies in clinical care of sarcoma patients. This chapter aims to give a brief overview of the most recent data available on the detection of circulating tumor cells and circulating tumor DNA in sarcomas.},
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pubstate = {published},
tppubtype = {inbook}
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Sarcomas are clustered in two oncological entities named bone and soft tissue sarcomas. Both are rare cancers originating from the mesenchyme, characterized by their propensity to induce the development of lung metastases. Sarcoma cells escaping from the primary tumor site spread to the pulmonary tissue through the bloodstream where they found a favorable microenvironment to establish metastatic foci. The low number of patients, the high histological, genetic, and molecular heterogeneity of sarcomas combined with the absence of specific markers expressed by cancer cells make the detection and follow-up of the minimal residual disease challenging. Over the last decade, tremendous technological progress has been made towards the detection of recurrent diseases. The literature is now enriched of information describing the use of liquid biopsies in clinical care of sarcoma patients. This chapter aims to give a brief overview of the most recent data available on the detection of circulating tumor cells and circulating tumor DNA in sarcomas.
Jubelin, Camille; Munoz-Garcia, Javier; Cochonneau, Denis; Moranton, Emilie; Heymann, Marie Françoise; Heymann, Dominique
Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma Article de journal
Dans: Cancer Drug Resistance, vol. 5, iss. 5, p. 184-198, 2022.
@article{jubelin2022biological,
title = {Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma},
author = {Camille Jubelin and Javier Munoz-Garcia and Denis Cochonneau and Emilie Moranton and Marie Françoise Heymann and Dominique Heymann},
doi = {10.20517/cdr.2021.130},
year = {2022},
date = {2022-02-16},
urldate = {2022-02-16},
journal = {Cancer Drug Resistance},
volume = {5},
issue = {5},
pages = {184-198},
abstract = {Sarcomas are a large family of cancers originating in the mesenchyme. Composed of more than 100 histological subtypes, soft tissue and bone sarcomas remain clinically challenging, particularly in children and adolescents in whom sarcomas are the second most common malignant entities. Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant. The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity. In the last decade, the notion of cancer stem-like cells (CSCs) has emerged. This subset of cancer cells has been linked to drug resistance properties, recurrence of the disease, and therapeutic failure. Although CSCs remain controversial, many elements are in favor of them playing a role in the development of the drug resistance profile. The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities. Their use as promising therapeutic targets is discussed.},
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pubstate = {published},
tppubtype = {article}
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Sarcomas are a large family of cancers originating in the mesenchyme. Composed of more than 100 histological subtypes, soft tissue and bone sarcomas remain clinically challenging, particularly in children and adolescents in whom sarcomas are the second most common malignant entities. Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant. The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity. In the last decade, the notion of cancer stem-like cells (CSCs) has emerged. This subset of cancer cells has been linked to drug resistance properties, recurrence of the disease, and therapeutic failure. Although CSCs remain controversial, many elements are in favor of them playing a role in the development of the drug resistance profile. The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities. Their use as promising therapeutic targets is discussed.
2022
Rabé, Marion; Fonteneau, Lucie; Oliver, Lisa; Morales-Molina, Alvaro; Jubelin, Camille; Garcia-Castro, Javier; Heymann, Dominique; Gratas, Catherine; Vallette, François M
Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment Article de journal
Dans: Frontiers in Cell and Developmental Biology, vol. 10, p. 975, 2022.
@article{rabe2022cellular,
title = {Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment},
author = {Marion Rabé and Lucie Fonteneau and Lisa Oliver and Alvaro Morales-Molina and Camille Jubelin and Javier Garcia-Castro and Dominique Heymann and Catherine Gratas and François M Vallette},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Frontiers in Cell and Developmental Biology},
volume = {10},
pages = {975},
publisher = {Frontiers},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2021
Muñoz-Garcia, Javier; Jubelin, Camille; Loussouarn, Aurélie; Goumard, Matisse; Griscom, Laurent; Renodon-Cornière, Axelle; Heymann, Marie-Françoise; Heymann, Dominique
In vitro three-dimensional cell cultures for bone sarcomas Article de journal
Dans: Journal of Bone Oncology, vol. 30, p. 100379, 2021, ISSN: 2212-1374.
@article{munoz2021vitro,
title = {In vitro three-dimensional cell cultures for bone sarcomas},
author = {Javier Muñoz-Garcia and Camille Jubelin and Aurélie Loussouarn and Matisse Goumard and Laurent Griscom and Axelle Renodon-Cornière and Marie-Françoise Heymann and Dominique Heymann},
editor = {Elsevier},
doi = {10.1016/j.jbo.2021.100379},
issn = {2212-1374},
year = {2021},
date = {2021-10-01},
urldate = {2021-10-01},
journal = {Journal of Bone Oncology},
volume = {30},
pages = {100379},
publisher = {Elsevier},
abstract = {Bone sarcomas are rare tumour entities that arise from the mesenchyme most of which are highly heterogeneous at the cellular, genetic and epigenetic levels. The three main types are osteosarcoma, Ewing sarcoma, and chondrosarcoma. These oncological entities are characterised by high morbidity and mortality and an absence of significant therapeutic improvement in the last four decades. In the field of oncology, in vitro cultures of cancer cells have been extensively used for drug screening unfortunately with limited success. Indeed, despite the massive knowledge acquired from conventional 2D culture methods, scientific community has been challenged by the loss of efficacy of drugs when moved to clinical trials. The recent explosion of new 3D culture methods is paving the way to more relevant in vitro models mimicking the in vivo tumour environment (e.g. bone structure) with biological responses close to the in vivo context. The present review gives a brief overview of the latest advances of the 3D culture methods used for studying primary bone sarcomas.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bone sarcomas are rare tumour entities that arise from the mesenchyme most of which are highly heterogeneous at the cellular, genetic and epigenetic levels. The three main types are osteosarcoma, Ewing sarcoma, and chondrosarcoma. These oncological entities are characterised by high morbidity and mortality and an absence of significant therapeutic improvement in the last four decades. In the field of oncology, in vitro cultures of cancer cells have been extensively used for drug screening unfortunately with limited success. Indeed, despite the massive knowledge acquired from conventional 2D culture methods, scientific community has been challenged by the loss of efficacy of drugs when moved to clinical trials. The recent explosion of new 3D culture methods is paving the way to more relevant in vitro models mimicking the in vivo tumour environment (e.g. bone structure) with biological responses close to the in vivo context. The present review gives a brief overview of the latest advances of the 3D culture methods used for studying primary bone sarcomas.