Side population cells isolated from human osteosarcoma are enriched with tumor-initiating cells

Cancer Sci. 2011 Oct;102(10):1774-81. doi: 10.1111/j.1349-7006.2011.02028.x. Epub 2011 Aug 3.

Abstract

It has been proven that "side population (SP)" cells that exclude Hoechst 33342 dye are enriched with cancer stem cells in several tumors. In the present study we aimed to isolate and characterize SP cells from human primary osteosarcoma. Side population cells were detected in osteosarcoma samples. In vitro, SP cells regenerated both SP and non-SP and the clonogenicity of SP cells was higher than that of non-SP cells, just like stem cells. In vivo, SP cells exhibited heightened tumorigenicity and only the SP fraction had the capacity to self- renew both in vitro and in vivo. Furthermore, SP cells exhibited increased multidrug resistance and the RNA expression of ATP-binding cassette protein transporters was increased in the SP group. In addition, "stemness" genes Oct-4 and Nanog were also upregulated in the SP group. However, the expression of other putative stem cell markers (CD44, CD117 and CD133) had no significant difference between SP and non-SP for each individual marker. These findings suggest that SP cells derived from osteosarcoma are enriched with tumorigenic cells with stem-like properties and might be an ideal target for clinical therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • ATP-Binding Cassette Transporters / biosynthesis
  • Animals
  • Antigens, CD / biosynthesis
  • Biomarkers, Tumor / biosynthesis
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology*
  • Drug Resistance, Neoplasm
  • Female
  • Glycoproteins / biosynthesis
  • Homeodomain Proteins / biosynthesis
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nanog Homeobox Protein
  • Neoplastic Stem Cells* / cytology
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Octamer Transcription Factor-3 / biosynthesis
  • Oligonucleotide Array Sequence Analysis
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology*
  • Peptides
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Side-Population Cells* / cytology
  • Side-Population Cells* / metabolism
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • AC133 Antigen
  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • Biomarkers, Tumor
  • Glycoproteins
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Proto-Oncogene Proteins c-kit