Immunohistochemical expression of stem cell, endothelial cell, and chemosensitivity markers in primary glioma spheroids cultured in serum-containing and serum-free medium

Neurosurgery. 2010 May;66(5):933-47. doi: 10.1227/01.NEU.0000368393.45935.46.

Abstract

Objective: To investigate the influence of serum-free medium (SFM) supplemented with epidermal growth factor and basic fibroblast growth factor compared with conventional serum-containing medium (SCM) on the phenotype of organotypic primary spheroids from seven gliomas.

Methods: Paraffin sections of the original surgical specimens, primary glioma spheroids, and U87 derived spheroids were stained immunohistochemically with the stem cell markers CD133, podoplanin, Sox2, Bmi-1, and nestin; the endothelial cell markers CD31, CD34, and Von Willebrand Factor (VWF); the chemosensitivity markers P-glycoprotein and tissue inhibitor of metalloproteinases-1 (TIMP-1); and glial fibrillary acidic protein, neural cell adhesion molecule CD56, and the proliferation marker Ki67.

Results: Scoring of the immunohistochemical stainings showed that the expression of CD133 and all other markers included was preserved in primary spheroids, confirming the in vivo-like nature of these spheroids. Spheroids in SFM better mimicked the in vivo phenotype with significantly more CD133, CD34, VWF, P-glycoprotein, TIMP-1, and Ki67 compared with SCM.

Conclusion: In this first study of the influence of SFM on primary glioma spheroids, the conditions favored an in vivo-like phenotype with increased expression of CD133. More vascular structures were found in SFM, suggesting that the close relationship between blood vessels and tumor stem-like cells was better preserved in this medium.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / metabolism*
  • Cell Culture Techniques / methods*
  • Culture Media
  • Culture Media, Serum-Free / pharmacology*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Epidermal Growth Factor / pharmacology
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Glioma / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Phenotype
  • Spheroids, Cellular / cytology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Culture Media
  • Culture Media, Serum-Free
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor