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New model of
tumor angiogenesis: dynamic balance between vessel regression and
growth mediated by angiopoietins and VEGF
Holash J, Wiegand SJ, Yancopoulos GD
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road,
Tarrytown, New York, NY 10591, USA.
Our analyses in several different tumor settings challenge the
prevailing view that malignancies and metastases generally
initiate as avascular masses that only belatedly induce vascular
support.
Instead, we find that malignant cells rapidly co-opt existing host
vessels to form an initially well-vascularized tumor mass.
Paradoxically, the co-opted vasculature does not undergo
angiogenesis to support the growing tumor, but instead regresses
(perhaps as part of a normal host defense mechanism) via a process
that involves disruption of endothelial cell/smooth muscle cell
interactions and endothelial cell apoptosis.
This vessel regression in turn results in necrosis within the
central part of the tumor.
However, robust angiogenesis is initiated at the tumor margin,
rescuing the surviving tumor and supporting further growth.
The expression patterns of Angiopoietin-2 (the natural antagonist
for the angiogenic Tie2 receptor) and vascular endothelial growth
factor (VEGF) strongly implicate these factors in the above
processes.
Angiopoietin-2 is highly induced in co-opted vessels, prior to
VEGF induction in the adjacent tumor cells, providing perhaps the
earliest marker of tumor vasculature and apparently marking the
co-opted vessels for regression.
Subsequently, VEGF upregulation coincident with Angiopoietin-2
expression at the tumor periphery is associated with robust
angiogenesis.
Thus, in tumors, Angiopoietin-2 and VEGF seem to reprise the roles
they play during vascular remodeling in normal tissues, acting to
regulate the previously underappreciated balance between vascular
regression and growth.
PMID: 10498889 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10498889
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