Effects of targeting the VEGF and PDGF pathways in diffuse orthotopic glioma models.

Autor: Navis AC; Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Hamans BC, Claes A, Heerschap A, Jeuken JW, Wesseling P, Leenders WP
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2011 Apr; Vol. 223 (5), pp. 626-34. Date of Electronic Publication: 2011 Feb 21.
DOI: 10.1002/path.2836
Abstrakt: Currently available compounds that interfere with VEGF-A signalling effectively inhibit angiogenesis in gliomas, but influence diffuse infiltrative growth to a much lesser extent. Development of a functional tumour vascular bed not only involves VEGF-A but also requires platelet-derived growth factor receptor-β (PDGFRβ), which induces maturation of tumour blood vessels. Therefore, we tested whether combined inhibition of VEGFR and PDGFRβ increases therapeutic benefit in the orthotopic glioma xenograft models E98 and E473, both displaying the diffuse infiltrative growth that is characteristically observed in most human gliomas. We used bevacizumab and vandetanib as VEGF(R) inhibitors, and sunitinib to additionally target PDGFRβ. We show that combination therapy of sunitinib and vandetanib does not improve therapeutic efficacy compared to treatment with sunitinib, vandetanib or bevacizumab alone. Furthermore, all compounds induced reduction of vessel leakage in compact E98 tumour areas, resulting in decreased detectability of these mostly infiltrative xenografts in Gd-DTPA-enhanced MRI scans. These data show that inhibition of VEGF signalling cannot be optimized by additional PDGFR inhibition and support the concept that diffuse infiltrative areas in gliomas are resistant to anti-angiogenic therapy.
(Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
Databáze: MEDLINE
Externí odkaz: