U-CH17P, -M and -S, a New Cell Culture System for Tumor Diversity and Progression in Chordoma

Int J Cancer. 2018 Apr 1;142(7):1369-1378. doi: 10.1002/ijc.31161. Epub 2017 Nov 27.

Abstract

Chordoma is a rare bone tumor with a known intrinsic heterogeneity. Here, we address this tumor heterogeneity in a new cell culture model for tumor 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 tumor tissues revealed that the precursor cells of U-CH17P, U-CH17M and U-CH17S were already present in the primary tumor. Therefore, we show that clonal diversity of this chordoma exists in the primary tumor 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 tumor progression in chordoma are still largely unclear, the three U-CH17 cell lines are a suitable in vitro model for elucidating chordoma oncobiology.

Keywords: cell lines; chordoma; tumor diversity; tumor progression.

MeSH terms

  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor / cytology*
  • Chordoma* / genetics
  • Chordoma* / pathology
  • Disease Progression
  • Humans