Pro-angiogenic signaling by the endothelial presence of CEACAM1.
Here, we demonstrate the expression of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in angiogenic sprouts but not in large mother blood vessels within tumor tissue. Correspondingly, only human microvascular endothelial cells involved in in vitro tube formation exhibit CEACAM1. CEACAM1-overexpressing versus CEACAM1-silenced human microvascular endothelial cells were used in migration and tube formation assays. CEACAM1-overexpressing microvascular endothelial cells showed prolonged survival and increased tube formation when they were stimulated with vascular endothelial growth factor (VEGF), whereas CEACAM1 silencing via small interfering RNA blocks these effects. Gene array and LightCycler analyses show an up-regulation of angiogenic factors such as VEGF, VEGF receptor 2, angiopoietin-1, angiopoietin-2, tie-2, angiogenin, and interleukin-8 but a down-regulation of collagen XVIII/endostatin and Tie-1 in CEACAM1-overexpressing microvascular endothelial cells. Western blot analyses confirm these results for VEGF and endostatin at the protein level. These results suggest that constitutive expression of CEACAM1 in microvascular endothelial cells switches them to an angiogenic phenotype, whereas CEACAM1 silencing apparently abrogates the VEGF-induced morphogenetic effects during capillary formation. Thus, strategies targeting the endothelial up-regulation of CEACAM1 might be promising for antiangiogenic tumor therapy.
Kilic
Nerbil
N
Institute of Anatomy, Medical Clinic I, University Hospital Eppendorf, D-20246 Hamburg, Germany.
Oliveira-Ferrer
Leticia
L
Wurmbach
Jan-Henner
JH
Loges
Sonja
S
Chalajour
Fariba
F
Neshat-Vahid
Samira
S
Vahid
Samira Neshat
SN
Weil
Joachim
J
Fernando
Malkanthi
M
Ergun
Suleyman
S
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D043170:Collagen Type XVIII / Q000502:physiology; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology; D043169:Endostatins / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042810:Receptor, TIE-1 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D043170:Collagen Type XVIII; D017931:DNA Primers; D043169:Endostatins; D042810:Receptor, TIE-1