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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 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 Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kilic, N. Articles by Ergün, S. Search for Related Content PubMed PubMed Citation Articles by Kilic, N. Articles by Ergün, S. Related Collections Cell Adhesion and Motility Free Research Articles Hematopoiesis Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Lymphatic reprogramming of microvascular endothelial cells by CEA-related cell adhesion molecule-1 via interaction with VEGFR-3 and Prox1 Nerbil Kilic1,2, Leticia Oliveira-Ferrer2,3, Samira Neshat-Vahid2, Ster Irmak3, Kirstin Obst-Pernberg3, Jan-Henner Wurmbach2, Sonja Loges1, Ergin Kilic4, Joachim Weil5, Heidrun Lauke3, Derya Tilki6, Bernhard B. Singer3, and Süleyman Ergün3 1 Internal Medicine, Department of Hematology/Oncology/Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg; 2 Institute of Anatomy, University Hospital Hamburg-Eppendorf, Hamburg; 3 Institute of Anatomy I, University Hospital Essen, Essen; 4 Department of Pathology, University Hospital Hamburg-Eppendorf, Hamburg; 5 Department of Cardiology, University Hospital Lübeck, Lübeck; and 6 Department of Urology, University Hospital Groβhadern, Munich, Germany Here, we demonstrate that carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed and co-localized with podoplanin in lymphatic endothelial cells (LECs) of tumor but not of normal tissue. CEACAM1 overexpression in human dermal microvascular endothelial cells (HDMECs) results in a significant increase of podoplanin-positive cells in fluorescence-activated cell sorting analyses, while such effects are not observed in CEACAM1 overexpressing human umbilical vein endothelial cell (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 vascular endothelial growth factor C, -D (VEGF-C, -D) and their receptor vascular endothelial growth factor receptor 3 (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 small interfering RNA 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]

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