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Invasion as
limitation to anti-angiogenic glioma therapy
Lamszus
K, Kunkel P, Westphal M
Department
of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg,
Germany. lamszus@uke.uni-hamburg.de
The inhibition of tumor angiogenesis could be an efficient
therapeutic strategy for the treatment of malignant gliomas.
Prominent neovascularization is induced by these tumors, and
microvascular proliferation is a malignancy grading
criterion.
However, glioma cells can also invade the brain diffusely over
long distances without necessarily requiring angiogenesis.
Experimentally, it was shown that especially during early stages
of growth in rodent brain, glioma cells can coopt the preexistent
host vasculature to recruit their blood supply in the absence of
neovascularization.
This phenomenon was only observed in orthotopic models in which
the tumor cells were implanted into the brain which is a densely
vascularized environment, but not in subcutaneous models in which
tumor cells are implanted into a virtual space.
Using an orthotopic mouse model, we analyzed whether systemic
anti-angiogenic therapy with an antibody against the vascular
endothelial growth factor receptor-2 (VEGFR-2) could inhibit
intracerebral growth of xenografted human glioblastoma cells and
what effect this treatment had on tumor morphology and
invasiveness.
We found that anti-angiogenic therapy inhibited tumor growth by
80% compared to buffer-treated controls.
The intratumoral microvessel density was reduced by at least 40%
in treated animals compared to controls.
However, in mice treated with the anti-VEGFR-2 antibody, we
noticed a striking increase in the number and total area of small
satellite tumors clustered around the primary mass.
These satellites usually contained central vessel cores, and tumor
cells often had migrated along blood vessels over long distances
to eventually reach the surface and spread in the subarachnoid
space.
Systemic anti-angiogenic therapy can thus apparently increase the
invasiveness of gliomas in the orthotopic model.
Tumor cell invasion was tightly associated with preexistent blood
vessels, suggesting that increased cooption of the host
vasculature could represent a compensatory mechanism that is
selected for by inhibiting adequate tumor vascularization.
PMID: 14531575 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14531575
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