Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 8, pp 1425–1431

Cilengitide response in ultra-low passage glioblastoma cell lines: relation to molecular markers

  • Christina S. Mullins
  • Julia Schubert
  • Björn Schneider
  • Michael Linnebacher
  • Carl F. Classen
Original Paper

DOI: 10.1007/s00432-013-1457-6

Cite this article as:
Mullins, C.S., Schubert, J., Schneider, B. et al. J Cancer Res Clin Oncol (2013) 139: 1425. doi:10.1007/s00432-013-1457-6

Abstract

Purpose

In glioblastoma multiforme (GBM), a tumor still characterized by dismal prognosis, recent research focuses on novel-targeted compounds, in addition to standard temozolomide (TMZ) chemotherapy. One of these emerging compounds is cilengitide (CGT), which by binding to integrins (i.e., αvβ3 and αvβ5) may inhibit angiogenesis and also is directly cytotoxic to tumor cells by interfering with intracellular signaling pathways.

Methods

A total of ten patient-derived ultra-low passage GBM cell lines were treated with increasing doses of CGT, TMZ, and a combination of both substances. Inhibitory concentrations of 50 % (IC50) were determined for the single agents and as a combination. Cell lines were stratified according to MGMT promoter methylation. The expression of relevant integrins was assessed by flow cytometry.

Results

In monotherapy, all GBM cell lines showed higher sensitivity to CGT than to TMZ, as determined by IC50 values in relation to clinically relevant patient plasma levels. MGMT promoter methylation correlated with a significantly higher TMZ response, but tended to be associated with a lower CGT response. Response to CGT was not correlated with cell surface integrin expression as measured by flow cytometry. Finally, addition of CGT to TMZ enhanced growth inhibition, but only in those cell lines with a methylated MGMT promoter.

Conclusions

As suggested by this analysis, patients with MGMT promoter-methylated GBM may benefit from addition of CGT to the standard TMZ treatment, while patients with MGMT promoter-unmethylated GBM may better respond to CGT monotherapy.

Keywords

Glioblastoma Ultra-low passage cell lines Response-prediction Integrins Cilengitide Temozolomide 

Abbreviations

CGT

Cilengitide

DMSO

Dimethyl Sulfoxide

GBM

Glioblastoma multiforme

IC50

Inhibitory concentrations of 50 %

MGMT

O6-Methylguanine-Methyltransferase

PBS

Phosphate-Buffered Saline

RGD

Arginine-glycine-aspartic acid

TMZ

Temozolomide

VEGF

Vascular endothelial growth factor

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christina S. Mullins
    • 1
    • 2
  • Julia Schubert
    • 1
  • Björn Schneider
    • 3
  • Michael Linnebacher
    • 2
  • Carl F. Classen
    • 1
  1. 1.University Children’s HospitalUniversity MedicineRostockGermany
  2. 2.Department of SurgeryUniversity MedicineRostockGermany
  3. 3.Department of PathologyUniversity MedicineRostockGermany

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