Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2007-12-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/CD66 antigens, http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/PDPN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor..., http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors, http://linkedlifedata.com/resource/pubmed/chemical/prospero-related homeobox 1 protein
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4223-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17761831-Antigens, CD, pubmed-meshheading:17761831-Cell Adhesion Molecules, pubmed-meshheading:17761831-Cell Lineage, pubmed-meshheading:17761831-Cells, Cultured, pubmed-meshheading:17761831-Endothelial Cells, pubmed-meshheading:17761831-Endothelium, Lymphatic, pubmed-meshheading:17761831-Endothelium, Vascular, pubmed-meshheading:17761831-Homeodomain Proteins, pubmed-meshheading:17761831-Humans, pubmed-meshheading:17761831-Lymphangiogenesis, pubmed-meshheading:17761831-Membrane Glycoproteins, pubmed-meshheading:17761831-Microcirculation, pubmed-meshheading:17761831-Protein Binding, pubmed-meshheading:17761831-RNA, Messenger, pubmed-meshheading:17761831-Skin, pubmed-meshheading:17761831-Tumor Suppressor Proteins, pubmed-meshheading:17761831-Umbilical Veins, pubmed-meshheading:17761831-Vascular Endothelial Growth Factor Receptor-3, pubmed-meshheading:17761831-Vascular Endothelial Growth Factors
pubmed:year
2007
pubmed:articleTitle
Lymphatic reprogramming of microvascular endothelial cells by CEA-related cell adhesion molecule-1 via interaction with VEGFR-3 and Prox1.
pubmed:affiliation
Internal Medicine, Department of Hematology/Oncology/Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't