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Growth factor receptors signaling in glioblastoma cells: therapeutic implications

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

In this study, we investigated the protein expression of platelet-derived growth factor receptor (PDGFR), insulin like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK1/2) in five primary glioblastoma (GB), with a view to their possible use as therapeutic targets. Our results demonstrated that appreciable levels of these proteins could be detected in the analysed GB cell lines, except for a low level of PDGFR and ERK1/2 expression in one GB cell line. The small molecule inhibitors towards IGF-1R, PDGFR, PI3-K and ERK1/2 respectively, have only modest or no anti-tumour activity on GB cells and therefore their combination with other therapy modalities was analysed. The interaction between small inhibitors and radiation was mostly additive or sub-additive; synergistic interaction was found in five of forty analysed combinations. Our results showed that GB cells are in general resistant to treatment and illustrate the difficulties in predicting the treatment response in malignant gliomas.

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Abbreviations

IGF-1R:

Insulin like growth factor-1 receptor

PDGFR:

Platelet derived growth factor receptor

PI3-K:

Phosphatidylinositol 3-kinase

MEK:

Mitogen/extracellular signal-regulated kinase

ERK:

Extracellularsignal-regulated kinase

GB:

Glioblastoma

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Acknowledgments

Grant sponsor: European Commission grant QLGA-CT-2000-60005; Cancer and Allergy Foundation, Stockholm; CNMP 41–063 Bucharest; Swedish Society of Medicine and The National Board of Health and Welfare Stockholm.

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Authors and Affiliations

  1. Department of Oncology-Pathology, Cancer Center Karolinska and Radiumhemmet Karolinska Institute/University Hospital, R8:00, 171 76, Stockholm, Sweden

    Mia Carapancea, Juan Castro, Magnus L. Bäcklund, Rolf Lewensohn & Anica Dricu

  2. University of Medicine and Pharmacy, Craiova, Romania

    Oana Alexandru, Ani S. Fetea, Laura Dragutescu & Anica Dricu

  3. Medico Science SRL, Bucharest, Romania

    Ada Georgescu

  4. Clinic of Neurology, Ernst Moritz Arndt University Greifswald, Greifswald, Germany

    A. Popa-Wagner

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  1. Mia Carapancea
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Correspondence to Anica Dricu.

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Carapancea, M., Alexandru, O., Fetea, A.S. et al. Growth factor receptors signaling in glioblastoma cells: therapeutic implications. J Neurooncol 92, 137–147 (2009). https://doi.org/10.1007/s11060-008-9753-8

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