Research line 1Gene
expression profiling of tumor endothelium
The main aim of research line I is to gain more insight in the gene expression changes
that occur during angiogenesis and to identify novel therapeutic targets for
anti-angiogenic therapy.
Gene expression profiling of tumor angiogenesis
Molecules distinguishing normal endothelial cells from tumor endothelial cells can be
identified by means of gene expression profiling techniques. Several studies have
described genes whose expression is changed in endothelial cells upon treatment with
different angiogenic factors in vitro. However, in vitro models do not accurately
represent the complex microenvironmental features normally present in vivo. Therefore,
endothelial cells isolated directly from tissues are the preferred source for these
studies.
Our mission is to identify specific molecular changes on tumor endothelial cells that
not only distuinguish them from normal, resting endothelial cells but also from
physiologically activated endothelial cells. This enables the design and application of
targeted therapies aimed at the tumor endothelial cell specifically, without interfering
with physiological angiogenesis.
From: van Beijnum et al. Blood, 2006.
Angiosuppressor genes and methylation
We have demonstrated that epigenetics are
involved in the regulation of angiogenesis. DNMT
inhibitors are antiproliferative for tumor-conditioned EC. We
show that DNMT inhibitors have angiostatic activity
in addition to their inhibitory effects on tumor cells.
This dual action of these compounds makes them promising anticancer
therapeutics.
In
addition, we
found that DNMT inhibitors 5-aza-2’-deoxycytidine and zebularine, as
well as HDAC inhibitor trichostatin A, re-expressed ICAM-1 on
tumor-conditioned EC in vitro, resulting in restored leukocyte-EC
adhesion.
From: Hellebrekers et al. Cancer Res, 2006 |
