Reduced expression of INK4a/ARF genes in stem-like sphere cells from rat sarcomas

Biochem Biophys Res Commun. 2007 Oct 26;362(3):773-8. doi: 10.1016/j.bbrc.2007.08.067. Epub 2007 Aug 22.

Abstract

The presence of cancer stem cells, in both hematopoietic and solid malignancies, has been recently linked to their pathogenesis. We aimed to identify the characteristics and stem-like properties of sphere-colony forming cells in rat osteosarcoma and malignant fibrous histiocytoma cell lines. The results showed that both cell lines possessed an ability to form spherical, clonally expanding colonies in anchorage-independent, serum-starved conditions in N2/1% methylcellulose medium. The sphere cells showed stem-like properties with the ability to self-renew, and expressed the stem cell-related STAT3 and Bmi1 genes. Interestingly, spheres from both sarcomas remarkably decreased the expression of INK4a/ARF locus genes, p16(INK4a) and p19(ARF), which could be related to the resistance against cell senescence and apoptosis. Spheres showed strong tumorigenicity with metastatic potential in vivo via the inoculation into syngeneic rats, suggesting the presence of these populations might contribute to the tumor development such as metastasis via the resistance to apoptotic stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16 / chemistry*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Primers / chemistry
  • Gene Expression Regulation, Neoplastic*
  • Histiocytoma, Malignant Fibrous / metabolism
  • Microscopy, Phase-Contrast
  • Neoplasm Metastasis
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Phenotype
  • Rats
  • STAT3 Transcription Factor / metabolism
  • Sarcoma / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Tumor Suppressor Protein p14ARF / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Primers
  • STAT3 Transcription Factor
  • Tumor Suppressor Protein p14ARF
  • p19(ARF) protein, rat