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Open Access Research article

Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

Jolieke G van Oosterwijk1, Danielle de Jong2, Maayke AJH van Ruler1, Pancras CW Hogendoorn1, PD Sander Dijkstra3, Carla SP van Rijswijk4, Isidro Machado5, Antonio Llombart-Bosch5, Karoly Szuhai2 and Judith VMG Bovée1*

Author Affiliations

1 Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

2 Department of Medical Cell Biology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

3 Department of Orthopedic surgery, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

4 Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands

5 Department of Pathology, University of Valencia Medical School, Avda, Blasco Ibañez 17, 46010, Valencia, Spain

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BMC Cancer 2012, 12:375  doi:10.1186/1471-2407-12-375

Published: 28 August 2012

Abstract

Background

Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.

Methods

We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.

Results

We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.

Conclusions

Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies.

Keywords:
Bone neoplasm; Chondrosarcoma; Cell line; IDH1; IDH2; p16