Gottfried, E. and Kreutz, M. and Haffner, S. and Holler, E. and Iacobelli, M. and Andreesen, Reinhard and Eissner, G. (2007) Differentiation of human tumour-associated dendritic cells into endothelial-like cells: an alternative pathway of tumour angiogenesis. Scandinavian journal of immunology 65 (4), pp. 329-35.
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Until recently, the only accepted mechanism of tumour vascularization was the sprouting of endothelial cells (EC) from pre-existing vessels, while recent studies suggest the contribution of stem cell-derived endothelial progenitors as well as cells from the myeloid lineage. Here, we show a new way of endothelial differentiation that involves the specific modulation of monocytes by the tumour environment. The tumour milieu is characterized by the presence of cytokines and lactate which induce the differentiation of tumour-invading monocytes into tumour-associated dendritic cells (DC). Additional incubation of tumour-associated DC with pro-angiogenic factors, such as vascular endothelial growth factor and oncostatin M, led to transdifferentiation into endothelial-like cells. The cells showed strong expression of von Willebrand factor and VE-Cadherin, both classical EC markers, while leukocytic markers were reduced. In addition, they were able to form network-like structures on matrigel, which could be blocked by the DNA-based drug Defibrotide. This finding may be of great therapeutic relevance for tumour therapy.
|Institutions:||Medicine > Abteilung für Hämatologie und Internistische Onkologie|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||20 Apr 2010 09:26|
|Last Modified:||20 Apr 2010 09:26|