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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4223-4233. Prepublished online as a Blood First Edition Paper on August 30, 2007; DOI 10.1182/blood-2007-06-097592. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-06-097592v1 110/13/4223    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kilic, N. Articles by Ergun, S. Search for Related Content PubMed PubMed Citation Articles by Kilic, N. Articles by Ergun, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 25, 2007 Accepted August 24, 2007 Lymphatic reprogramming of micro vascular endothelial cells by CEA-related Cell Adhesion Molecule-1 via interaction with VEGFR-3 and Prox1 Nerbil Kilic, Leticia Oliveira-Ferrer, Samira Neshat-Vahid, Ster Irmak, Kirstin Obst-Pernberg, Jan-Henner Wurmbach, Sonja Loges, Ergin Kilic, Joachim Weil, Heidrun Lauke, Derya Tilki, Bernhard B Singer, and Suleyman Ergun* Internal Medicine, Department of Hematology/Oncology/Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany Institute of Anatomy I, University Hospital Essen, Essen, Germany Institute of Anatomy, University Hospital Hamburg-Eppendorf, Hamburg, Germany Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg, Germany Department of Cardiology, University Hospital Lubeck, Lubeck, Germany Department of Urology, University Hospital Grosshadern, Munich, Germany * Corresponding author; email: sueleyman.erguen{at}uk-essen.de. Here, we demonstrate that CEACAM1 is expressed and co-localized with podoplanin in lymphatic endothelial cells (LECs) of tumor but not of normal tissue. CEACAM1 overexpression in HDMECs results in a significant increase of podoplanin positive cells in FACS analyses while such effects are not observed in CEACAM1 overexpressing HUVECs. This effect of CEACAM1 is ceased when HDMECs are transfected with CEACAM1/y-- missing the tyrosine residues in its cytoplasmic domain. CEACAM1 overexpression in HDMECs leads to an up-regulation of VEGF-C, -D and their receptor VEGFR-3 at mRNA and protein levels. HDMECs transfected with CEACAM1 but not those with CEACAM1/y-- show enhanced expression of the lymphatic markers Prox1, Podoplanin and LYVE-1. Furthermore, Prox1 silencing in HDMECs via siRNA blocks the CEACAM1-induced increase of VEGFR-3 expression. Number and network of endothelial tubes induced by VEGF-C and -D are enhanced in CEACAM1-overexpressing HDMECs. Moreover, VEGF-A treatment of CEACAM1-silenced HDMECs restores their survival but not that with VEGF-C- and VEGF-D. These data imply that the interaction of CEACAM1 with Prox1 and VEGFR-3 plays a crucial role in tumor lymphangiogenesis and reprogramming of vascular endothelial cells to LECs. CEACAM1-induced signaling effects appear to be dependent on the presence of tyrosine residues in the CEACAM1 cytoplasmic domain. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Is CEACAM1 a lymphangiogenic switch? Björn Öbrink Blood 2007 110: 4137-4138. [Full Text] [PDF] This article has been cited by other articles: A. K. Horst, T. Bickert, N. Brewig, P. Ludewig, N. van Rooijen, U. Schumacher, N. Beauchemin, W. D. Ito, B. Fleischer, C. Wagener, et al. CEACAM1+ myeloid cells control angiogenesis in inflammation Blood, June 25, 2009; 113(26): 6726 - 6736. [Abstract] [Full Text] [PDF]

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