Genetically transforming human mesenchymal stem cells to sarcomas: Changes in cellular phenotype and multilineage differentiation potential

Nan Li, Rui Yang, Wendong Zhang, Howard Dorfman, Pulivarthi Rao, Richard Gorlick

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

BACKGROUND: The cell of origin of sarcoma is still unclear. High-grade osteosarcomas frequently demonstrate the potential for multipotent differentiation and, along with several other lines of evidence, suggest that human mesenchymal stem cells (hMSC) might be the cell of origin. METHODS: The hMSCs were transformed with retrovirus containing human telomerase reverse transcriptase (hTERT), simian virus 40 large t antigen (SV40 TAg), and lentivirus containing oncogenic H-Ras serially. The changes of cellular phenotypes and multilineage differentiation capacity were observed and compared with the standard osteosarcoma cell lines. RESULTS: Two distinct genotypic and phenotypic sarcoma cell lines resulted from the same genetic events. The gene expression profiles became more complicated and the karyotype became more chaotic during hMSCs' tumorigenesis. The motility of transformed hMSC was promoted. hMSC and its derivatives could be induced to osteogenic, adipogenic, and chondrogenic differentiation except that MSCTSR4 lost osteogenic differentiation capacity. CONCLUSIONS: Multilineage differentiation potential was retained during tumorigenesis of hMSCs and distinct sarcoma cell lines could arise with the same genetic events, providing good models in better understanding the concept of hMSC and in further investigation of the relationship of hMSCs and osteosarcomas.

Original languageEnglish (US)
Pages (from-to)4795-4806
Number of pages12
JournalCancer
Volume115
Issue number20
DOIs
StatePublished - Oct 15 2009

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Mesenchymal Stromal Cells
Sarcoma
Osteosarcoma
Phenotype
Cell Line
Carcinogenesis
Lentivirus
Simian virus 40
Retroviridae
Karyotype
Transcriptome
Antigens

Keywords

  • Human mesenchymal stem cell
  • Multilineage differentiation potential
  • Osteosarcoma
  • Tumorigenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetically transforming human mesenchymal stem cells to sarcomas : Changes in cellular phenotype and multilineage differentiation potential. / Li, Nan; Yang, Rui; Zhang, Wendong; Dorfman, Howard; Rao, Pulivarthi; Gorlick, Richard.

In: Cancer, Vol. 115, No. 20, 15.10.2009, p. 4795-4806.

Research output: Contribution to journalArticle

Li, Nan ; Yang, Rui ; Zhang, Wendong ; Dorfman, Howard ; Rao, Pulivarthi ; Gorlick, Richard. / Genetically transforming human mesenchymal stem cells to sarcomas : Changes in cellular phenotype and multilineage differentiation potential. In: Cancer. 2009 ; Vol. 115, No. 20. pp. 4795-4806.
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