Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic therapy in malignant gliomas

J Neurooncol. 2015 Jan;121(2):269-78. doi: 10.1007/s11060-014-1647-3. Epub 2014 Nov 5.

Abstract

Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can promote cancer growth by various mechanisms. Placenta growth factor is upregulated in many neoplastic diseases and serum levels of PlGF are increased in cancer patients following anti-angiogenic therapy. However, its role in glioma growth is yet not fully elucidated. In this study we analyzed the expression of PlGF mRNA using real time PCR in human gliomas of different WHO grades. Placenta growth factor mRNA levels were highly variable and did not correlate with WHO grades, arguing against a significant role in glioma progression. The highest PlGF expression was observed in anaplastic astrocytomas whereas grade II astrocytomas and glioblastomas displayed lower levels of expression. Immunohistochemical analysis showed that PlGF was expressed by inflammatory and endothelial cells in addition to tumor cells. Placenta growth factor mRNA expression in 12 matched glioblastoma samples before and after therapy, including bevacizumab and cilengitide treatment was largely unaffected by the aforementioned treatment modalities. In vitro, the exposure of VEGFR-1 expressing glioma cells to bevacizumab did not increase the expression levels of PlGF mRNA. In summary, our results do not support the hypothesis that PlGF plays a major role in the resistance of gliomas after anti-angiogenic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Biomarkers, Tumor / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / physiology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / surgery
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism*
  • Prognosis
  • RNA, Messenger / metabolism
  • Retrospective Studies
  • Snake Venoms / therapeutic use
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • PGF protein, human
  • Pregnancy Proteins
  • RNA, Messenger
  • Snake Venoms
  • Placenta Growth Factor
  • Bevacizumab
  • Cilengitide
  • Vascular Endothelial Growth Factor Receptor-1