Cilengitide inhibits proliferation and differentiation of human endothelial progenitor cells in vitro.
Bone marrow derived hematopoietic stem cells can function as endothelial progenitor cells. They are recruited to malignant tumors and differentiate into endothelial cells. This mechanism of neovascularization termed vasculogenesis is distinct from proliferation of pre-existing vessels. To better understand vasculogenesis we developed a cell culture model with expansion and subsequent endothelial differentiation of human CD133(+) progenitor cells in vitro. alpha(v)beta(3)-integrins are expressed by endothelial cells and play a role in the attachment of endothelial cells to the extracellular matrix. We investigated the effect of Cilengitide, a peptide-like, high affinity inhibitor of alpha(v)beta(3)- and alpha(v)beta(5)-integrins in our in vitro system. We could show expression of alpha(v)beta(3)-integrin on 60+/-9% of non-adherent endothelial progenitors and on 91+/-7% of differentiated endothelial cells. alpha(v)beta(3)-integrin was absent on CD133(+) hematopoietic stem cells. Cilengitide inhibited proliferation of CD133(+) cells in a dose-dependent manner. The development of adherent endothelial cells from expanded CD133(+) cells was reduced even stronger by Cilengitide underlining its effect on integrin mediated cell adhesion. Expression of endothelial antigens CD144 and von Willebrand factor on differentiating endothelial precursors was decreased by Cilengitide. In summary, Cilengitide inhibits proliferation and differentiation of human endothelial precursor cells underlining its anti-angiogenic effects.
Loges
Sonja
S
University Hospital Hamburg-Eppendorf, Department of Medicine, Hamburg, Germany.
Butzal
Martin
M
Otten
Jasmin
J
Schweizer
Michaela
M
Fischer
Uta
U
Bokemeyer
Carsten
C
Hossfeld
Dieter K
DK
Schuch
Gunter
G
Fiedler
Walter
W
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D012910:Snake Venoms / Q000008:administration & dosage*
D012910:Snake Venoms; C422910:Cilengitide