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New blood vessel formation in tumors is achieved by activation of already existing blood
vessels within the tissue and by recruitment of vascular progenitor cells and modulatory cells.
Vascular progenitor cells, which can be drafted from the bone marrow, differentiate then into
endothelial cells and pericytes to form a new vasculature. We were one of the first who
identified pericyte progenitors and demonstrated that these cells are capable of differentiating
into mature pericytes and elicit survival factors to endothelial cells. More recently, we
discovered a different vascular progenitor population in tumors that is not derived from the
bone marrow but activated within the tumor when angiogenesis occurs. These cells are less
committed because they appear to differentiate into endothelial cells and pericytes. Utilizing
transgenic and orthotopic mouse models of brain and pancreatic tumors, we intend to study the
exact nature and function, and recruitment mechanisms of the distinct vascular progenitor
populations in tumors and elicit the crucial signaling pathways that dictate dormancy, self-renewal
capacity and differentiation. The goal is to target these populations in tumors to improve antiangiogenic
therapy and to utilize them therapeutically in ischemic conditions. We further have started
to investigate the effects of the vascular niche in response to the onset of angiogenesis
on the maintenance and activation of tumor-initiating cells in tumors.
Selected Publications
Bergers G. and Benjamin L.E. (2003): The Angiogenic Switch in Tumorigenesis, Article for Nature Reviews Cancer 3: 401-410.
Blouw B., Song H., Tihan T., Bosze J., Ferrar N., Gerber H.-P., Johnson R.S. and Bergers G. (2003): The hypoxic response of tumors is dependent on their microenvironment. Cancer Cell 3: 347-361
Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G. (2005). "PDGFRbeta(+)
perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival". Nature Cell Biol. 9: 870-879.
Du, R, Lu, K., Petritsch, C, Liu, P, Ganss, R.,Passegue, E., Song, H., Werb, Z and Bergers, G. (2007). HIF/Hypoxia induces recruitment of BMD vascular modulatory cells to regulate angiogenesis and invasion in tumors. In revision in Cancer Cell
Information last updated September 2007
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