Elevated expression of VEGFR-3 in lymphatic endothelial cells from lymphangiomas.
BACKGROUND
Lymphangiomas are neoplasias of childhood. Their etiology is unknown and a causal therapy does not exist. The recent discovery of highly specific markers for lymphatic endothelial cells (LECs) has permitted their isolation and characterization, but expression levels and stability of molecular markers on LECs from healthy and lymphangioma tissues have not been studied yet. We addressed this problem by profiling LECs from normal dermis and two children suffering from lymphangioma, and also compared them with blood endothelial cells (BECs) from umbilical vein, aorta and myometrial microvessels.


METHODS
Lymphangioma tissue samples were obtained from two young patients suffering from lymphangioma in the axillary and upper arm region. Initially isolated with anti-CD31 (PECAM-1) antibodies, the cells were separated by FACS sorting and magnetic beads using anti-podoplanin and/or LYVE-1 antibodies. Characterization was performed by FACS analysis, immunofluorescence staining, ELISA and micro-array gene analysis.


RESULTS
LECs from foreskin and lymphangioma had an almost identical pattern of lymphendothelial markers such as podoplanin, Prox1, reelin, cMaf and integrin-alpha1 and -alpha9. However, LYVE-1 was down-regulated and VEGFR-2 and R-3 were up-regulated in lymphangiomas. Prox1 was constantly expressed in LECs but not in any of the BECs.


CONCLUSIONS
LECs from different sources express slightly variable molecular markers, but can always be distinguished from BECs by their Prox1 expression. High levels of VEGFR-3 and -2 seem to contribute to the etiology of lymphangiomas.
Norgall
Susanne
S
Department Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany. susannenorgall@gmx.de <susannenorgall@gmx.de>
Papoutsi
Maria
M
Rössler
Jochen
J
Schweigerer
Lothar
L
Wilting
Jörg
J
Weich
Herbert A
HA
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002648:Child; D042783:Endothelial Cells / Q000166:cytology; D004729:Endothelium, Lymphatic / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008202:Lymphangioma / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011379:Prognosis; D000091042:Reelin Protein; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D000091042:Reelin Protein; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; C000717127:RELN protein, human