Cripto-1 expression in glioblastoma multiforme

Brain Pathol. 2014 Jul;24(4):360-70. doi: 10.1111/bpa.12131. Epub 2014 Mar 28.

Abstract

Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto-1 (CR-1) has a key regulatory role in embryogenesis, while in adult tissue re-expression of CR-1 has been correlated to malignant progression in solid cancers of non-neuronal origin. As CR-1 expression has yet to be described in cerebral cancer and CR-1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR-1 in the context of expression in GBM. The study was performed using enzyme-linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low-grade glioma patients. Within the patient cohort, we found high CR-1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR-1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR-1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.

Keywords: CR-1; endothelial proliferation; glioblastoma multiforme; microvasculature; plasma biomarker; tumor niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers / metabolism
  • Blotting, Western
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • GPI-Linked Proteins / metabolism*
  • Glioblastoma / metabolism*
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Transplantation
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • TDGF1 protein, human