The expression of antisense vascular endothelial growth factor (VEGF) sequences inhibits intracranial C6 glioma growth in vivo by suppressing tumour angiogenesis.
Human gliomas, including astrocytomas, consist of highly heterogeneous populations of cells that represent different stages of malignancy. Glioblastoma multiforme is the most highly vascularised class of solid tumour. In order to develop efficacious adjuvant therapies for gliomas the growth pathway(s) targeted must be common to all of these tumours. As angiogenesis is a requirement for all solid tumour growth, we have targeted this process in order to suppress glioma growth in vivo. We have applied antisense VEGF gene expression to disrupt the VEGF/VEGF receptor paracrine pathway in C6 glioma cells and, thereby, inhibit tumour angiogenesis. C6 glioma cells which constitutively express antisense VEGF sequences were demonstrated to have significantly inhibited growth rates when implanted intracranially. Antisense VEGF expressing tumours had a markedly lower level of vascularisation which was accompanied by an increased level of necrosis compared to control tumours. Furthermore, these data support the notion that VEGF is the sole factor required for tumour angiogenesis as other potentially angiogenic factors could not compensate for the reduced level of VEGF expression in the antisense-VEGF expressing tumours. Our findings also suggest that the inhibition of angiogenesis is sufficient to significantly suppress tumour growth and is thus an effective point for therapeutic intervention for gliomas and all solid tumours.
Saleh
M
M
Neuroscience Research Laboratories, The Melbourne Neuroscience Centre, Departments of Surgery and Neurosurgery, The University of Melbourne and The Royal Melbourne Hospital, Melbourne, Australia.
Vasilopoulos
K
K
Stylli
S S
SS
Kaye
A H
AH
Wilks
A F
AF