ECTS2013 Poster Presentations Cancer and bone: basic, translational and clinical (31 abstracts)
New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance
David Monderer 1, , Alexandrine Luseau 2 , Amélie Bellec 3 , Emmanuelle David 1, , Stéphanie Ponsolle 3 , Soraya Saïagh 3 , Sylvain Bercegeay 3 , Philippe Piloquet 5 , Marc Denis 6 , Laurence Lodé 7 , Françoise Rédini 1, , Marine Biger 8 , Dominique Heymann 1, , Marie-Françoise Heymann 1, , Ronan Le Bot 2, , François Gouin 1, & Frédéric Blanchard 1
1Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes, INSERM, UMR 957, Equipe Labellisée LIGUE 2012, Nantes, France; 2Atlantic Bone Screen (ABS), St Herblain, France; 3Unit of Cell and Gene Therapy, Nantes University Hospital, Nantes, France; 4Atlanthera, St Herblain, France; 5Department of Medical Genetics, Nantes University Hospital, Nantes, France; 6Department of Biochemistry, Nantes University Hospital, Nantes, France; 7Hematology Laboratory, Nantes University Hospital, Nantes, France; 8Osteoarticular Diseases Unit, Nantes University Hospital, Nantes, France.
Chondrosarcomas are cartilage-forming, poorly vascularized tumors. With an estimated annual incidence of 1 in 200 000, they represent the second malignant primary bone tumor of adults after osteosarcoma. These tumors are resistant to chemotherapy and radiotherapy, surgical excision remaining the only therapeutic option. However, very few cell lines and animal models are available, and the mechanisms behind their chemoresistance remain largely unknown. Our goal was to establish new cell lines and animal cancer models from human chondrosarcoma biopsies. These models were then used to study chondrosarcoma chemoresistance.
During the last 5 years, 10 chondrosarcoma biopsies were collected at the Nantes hospital and used for cell culture and transplantation in Nude mice. Only one transplanted biopsy and one injected cell line developed in immunodeficient mice, producing conventional central high grade chondrosarcoma. In culture, three new cell lines were obtained from high grade chondrosarcoma biopsies. Their genetic characterization revealed (hyper)triploid karyotypes, mutations in IDH1, IDH2, TP53, deletion in P16INK4A / P14ARF and/or MDM2 amplification. These cell lines expressed mesenchymal membrane markers (CD44, 73, 90 and 105) and were able to produce a cartilaginous matrix only in 3D chondrogenic cultures. Using a high throughput quantitative RT-PCR approach, we observed that cell lines in monolayer culture (2D) lost expression of genes implicated in cartilage development (COL2A1, COMP, AGC, SOX5/6, etc.) but regained expression in 3D cultures. Chondrosarcoma cells in monolayer culture were not resistant to mafosfamide, cisplatin or doxorubicin but in 3D culture, they were resistant to low doses of cisplatin and doxorubicin. In fact, low doses of doxorubicin could not accumulate in chondrosarcoma cells when cultured in 3D, indicating that impaired diffusion of the drugs through the cartilaginous matrix would lead to chemoresistance. Therefore, 3D cell pellets constitute a relevant model to study chondrosarcoma chemoresistance and could be a valuable alternative to animal experimentations.
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Bone Abstracts
ISSN 2052-1219 (online)
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