The cells that form the inner lining of the blood vessels.
sturcture to which cells adhere
in cell culture
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Angiogenesis is the formation of new blood vessels form pre-existing vasculature. This occurs in the healthy body during wound healing or the growth of the endometrium. However, under pathological conditions abnormal angiogensis may occur. An example is the excess of angiogenesis in cancer (tumor growth).
Staining of mouse
green: blood vessel
red: extracellular matrix
In the 1970's the idea was born that tumor growth can be inhibited by targeting angiogenesis. Blocking tumor blood vessel growth deprives the tumor cells of nutirients and oxygen. Today there are several angiogensis inhibitors on the market for treatment of cancer. Most of these drugs target pro-angiogenesis signaling by tumor cells through neutralization of growth factors (e.g. anti-VEGF (vascular endothelial growth factor) antibodies like bevacizumab/Avastin), or by inhibiting kinase activity of the growth factor receptors (e.g. sunitinib/Sutent). Although these drugs experience (commercial) success, it is now becoming evident that these agents, in general, only have a moderate effect on survival rates of patients. Furthermore, these angiogenesis inhibitors show severe side effects in patients.
Specific targeting of the tumor blood vessels
We would like to develop a better and more specific anti-angiogenic therapy. Therefore, our approach is to identify novel specific markers of angiogenic tumor endothelium, which we can target with specific drugs. Advantages would be that this approach is independent of the growth factor production by tumor cells, reducing the risk of tumor cell mutation into drug resistant variants. In addition, if the identified targets are specific to the tumor endothelial cells, toxic side effects would be minimized.
Search for specific targets in the tumor blood vessels
Our idea is that certain genes with an exclusive function in the embryo also become expressed in the tumor vasculature. We have indeed identified several embryonic genes, which are switched on in tumor endothelial cells again, but are not present in the adult. Currently, we are performing target function experiments in vitro.
Identification of new targets in the tumor blood vessels for the development of anti-angiogenic drugs.
Cancer Center Amsterdam
Inhibition of angiogenesis as a strategy to inhibit tumor growth
Disclaimer: E. Huijbers, updated 15 October 2014