Establishment and proteomic characterization of patient-derived clear cell sarcoma xenografts and cell lines

Marimu Sakumoto, Rieko Oyama, Mami Takahashi, Yoko Takai, Fusako Kito, Kumiko Shiozawa, Zhiwei Qiao, Makoto Endo, Akihiko Yoshida, Akira Kawai, Tadashi Kondo

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Clear cell sarcoma (CCS) is an aggressive mesenchymal malignancy characterized by the unique chimeric EWS-ATF1 fusion gene. Patient-derived cancer models are essential tools for the understanding of tumorigenesis and the development of anti-cancer drugs; however, only a limited number of CCS cell lines exist. The objective of this study was to establish patient-derived CCS models. We established patient-derived CCS models from a 43-yr-old female patient. We prepared the patient-derived xenografts (PDXs) from tumor tissues obtained through biopsy or surgery and isolated stable cell lines from PDXs and the original tumor tissue. The presence of gene fusions was examined by RT-PCR, and Sanger sequencing. The established cell lines were characterized by short tandem repeat, viability, colony and spheroid formation, and invasion analyses. Differences in gene enrichment between the primary tumor and cell lines were examined by mass spectrometry and KEGG pathway analysis. The cell lines were maintained for more than 80 passages, and had tumorigenic characteristics such as colony and spheroid formation and invasion. Mass spectrometric proteome analysis demonstrated that the cell lines were enriched for similar but distinct molecular pathways, compared to those in the xenografts and original tumor tissue. Next, tyrosine kinase inhibitors were screened for their suppressive effects on viability. We found that ponatinib, vandetanib, and doxorubicin suppressed the growth of cell lines, and had equivalent IC50 values. Further in-depth investigation and understanding of drug-sensitivity mechanisms will be important for the clinical applications of our cell lines.

Original languageEnglish
Pages (from-to)163-176
Number of pages14
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume54
Issue number2
DOIs
Publication statusPublished - Feb 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

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