Expression and prognostic value of JAM-A in gliomas

J Neurooncol. 2017 Oct;135(1):107-117. doi: 10.1007/s11060-017-2555-0. Epub 2017 Jul 4.

Abstract

Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes, and the intensity was higher in glioblastomas than low-grade gliomas. We could not detect an association with overall survival in patients with grade II and III tumors. Double-immunofluorescence stainings in glioblastomas revealed co-expression of JAM-A with CD133, SOX2, nestin, and GFAP in tumor cells as well as some co-expression with the microglial/macrophage marker IBA-1. In conclusion, JAM-A expression was higher in glioblastomas compared to low-grade gliomas and co-localized with recognized stem cell markers suggesting an association of JAM-A with glioma aggressiveness. No significant association between JAM-A expression and overall survival was found in grade II and III gliomas. Further research is needed to determine the function and clinical impact of JAM-A in gliomas.

Keywords: Astrocytic brain tumors; Glioma; Junctional adhesion molecule-A; Prognosis; Tumor stem cell.

MeSH terms

  • AC133 Antigen / metabolism
  • Adult
  • Biomarkers, Tumor / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules / metabolism*
  • Cohort Studies
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Neoplasm Grading
  • Nestin
  • Prognosis
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism*
  • SOXB1 Transcription Factors / metabolism
  • Survival Analysis

Substances

  • AC133 Antigen
  • AIF1 protein, human
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • F11R protein, human
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • NES protein, human
  • Nestin
  • PROM1 protein, human
  • RNA, Messenger
  • Receptors, Cell Surface
  • SOX2 protein, human
  • SOXB1 Transcription Factors