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Frequent epigenetic alterations in polycomb repressive complex 2 in osteosarcoma cell lines

Helin Feng1, Heather Tillman2, Gang Wu3

  • 1Department of Orthopedics, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, People's Republic of China.

Oncotarget
|June 23, 2018
PubMed

Insights

Osteosarcoma cell lines frequently lack polycomb repressive complex 2 (PRC2) function, unlike tumor samples. This finding necessitates caution when using these cell lines for cancer research and drug screening.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Osteosarcoma (OS) cell lines are crucial for cancer research, target identification, and drug screening.
  • Understanding the epigenetic landscape of OS is vital for developing effective therapies.

Purpose of the Study:

  • To investigate the functional status of polycomb repressive complex 2 (PRC2) in osteosarcoma cell lines compared to tumor samples.
  • To assess the clinical relevance of PRC2 components, such as EZH2, in osteosarcoma patient survival.

Main Methods:

  • Genomic sequencing, Western blotting, and immunohistochemistry were used to analyze PRC2 function and H3K27me3 levels.
  • Kaplan-Meier analysis was performed to correlate EZH2 expression with metastasis-free survival in OS patients.

Main Results:

  • A frequent loss-of-function of PRC2 was observed in osteosarcoma cell lines, with U2OS and 143B showing complete loss.
  • In contrast, PRC2 dysfunction was rare in osteosarcoma tumor tissues, with only one sample showing low H3K27me3 expression.
  • High EZH2 expression was significantly associated with poor metastasis-free survival in osteosarcoma patients.

Conclusions:

  • Osteosarcoma cell lines exhibit frequent PRC2 loss-of-function, differing significantly from tumor samples.
  • Caution is advised when utilizing these cell lines for studying OS biology, target validation, and drug screening.
  • Despite limitations, these cell lines can serve as valuable tools for dissecting PRC2 functions in cancer.
Keywords:
EZH2H3K27me3osteosarcomapolycomb repressive complex 2

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