U-CH17P, -M, and -S, a new cell culture system for tumour diversity and progression in chordoma

Abstract

Chordoma is a rare bone tumour with a known intrinsic heterogeneity. Here, we address this tumour heterogeneity in a new cell culture model for tumour diversity and progression in chordoma. The three cell lines U-CH17P, U-CH17M, and U-CH17S were established from a primary sacral chordoma and its derived metastases, a soft tissue and a skin metastasis, respectively. The lesions had divergent differentiation patterns which are conserved in the derived cell lines making them a suitable in vitro model for the analysis of tumorigenesis in chordoma. A common feature of the three cell lines is the expression of typical chordoma markers, such as Brachyury, vimentin, cytokeratins, EMA, and S100 protein. A comparison of the genomic aberrations by array comparative genomic hybridization of the cell lines and the corresponding parental tumour tissues revealed that the precursor cells of U-CH17P, U-CH17M, and U-CH17S were already present in the primary tumour. Therefore, we show that clonal diversity of this chordoma exists in the primary tumour and that not all of these subclones tend to metastasize. All cell lines had a CDKN2A loss. A comparison of the gene expression profiles of the cell lines revealed significant differences in the expression of several genes like MAGEC2 and SEMA6A known to be associated with the tendency to metastasize or proliferation and migration. Since the underlying mechanisms of tumour progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology. This article is protected by copyright. All rights reserved.

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