Target- and drug discovery
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-angiogenesis therapy.
Molecules distinguishing normal endothelial cells from tumor endothelial cells can be identified by means of gene expression profiling techniques. Several studies have described gene expression changes 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, we established an isolation technique for the purification of endothelial cells from tumor tissues (Van Beijnum et al. Nature Protocols, 2008).
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.
We also study the function and application of galectins in endothelial cell biology and tumor angiogenesis. Galectins are a protein family that plays a role in different steps of tumor progression, including angiogenesis, immune escape, and metastasis (Thijssen, Blood, 2007). We have shown that multiple galectins are expressed by tumor endothelial cells (Thijssen, Am J Path, 2008). In addition, we found that inhibition of galectin-1 with the in-house developed angiostatic peptide anginex is an effective anti-cancer therapy (Thijssen, PNAS, 2006; Thijssen, Cancer Res, 2010).
Figure. Tumor-derived galectin-1 can compensate for the lack of galectin-1 in the tumor endothelium of gal-1−/− mice. A, overall tumor growth of two independent experiments with TC-1 lung carcinoma cells in gal-1wt and gal-1−/− mice. B, immunohistochemical vessel staining (brown) in TC-1 and F9 tumors in gal-1wt and gal-1−/− mice. Diagram on the right shows the quantification of MVD in TC-1 and F9 tumors in gal-1wt and gal-1−/− mice. C, immunohistochemical staining of galectin-1 (brown) in F9 and TC-1 tumors in gal-1wt mice (left) and gal-1−/− mice (right). Arrows, endothelial cells that are negative for galectin-1 in the F9 tumors and positive for galectin-1 in the TC-1 tumors. D, fluorescent microscopic images of endothelial cells cultured in the presence of gal-1OG488 (green). Left, control cells treated with unlabeled galectin-1. (From Thijssen et al. Cancer Res, 2010)