Molecular characterization of lymphatic endothelial cells.
The lymphatic microvasculature is uniquely adapted for the continuous removal of interstitial fluid and proteins and is an important entry point for leukocytes and tumor cells. Specialized functions of lymphatics suggest differences in the molecular composition of the lymphatic and blood vascular endothelium. However, the extent to which the two cell types differ is still unclear, and few molecules that are truly specific to lymphatic endothelial cells have been identified to date. We have isolated primary lymphatic and blood microvascular endothelial cells from human skin by immunoselection with the lymphatic marker LYVE-1 and demonstrate that the two cell lineages express distinct sets of vascular markers and respond differently to growth factors and extracellular matrix. Comparative microarray analysis of gene-expression profiles revealed a number of unique molecular properties that distinguish lymphatic and blood vascular endothelium. The molecular profile of lymphatic endothelium seems to reflect characteristic functional and structural features of the lymphatic capillaries. Classification of the differentially expressed genes into functional groups revealed particularly high levels of genes implicated in protein sorting and trafficking, indicating a more active role of lymphatic endothelium in uptake and transport of molecules than previously anticipated. The identification of a large number of genes selectively expressed by lymphatic endothelium should facilitate the discovery of hitherto unknown lymphatic vessel markers and provide a basis for the analysis of the molecular mechanisms accounting for the characteristic functions of lymphatic capillaries.
Podgrabinska
Simona
S
Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Braun
Pascal
P
Velasco
Paula
P
Kloos
Bryan
B
Pepper
Michael S
MS
Skobe
Mihaela
M
D015415:Biomarkers; D019070:Cell Lineage; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004729:Endothelium, Lymphatic / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D051191:Plakophilins; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011506:Proteins / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis; D033921:Vesicular Transport Proteins
D015415:Biomarkers; D016228:Endothelial Growth Factors; D006023:Glycoproteins; C119248:LYVE1 protein, human; D051191:Plakophilins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011506:Proteins; D042582:Vascular Endothelial Growth Factor C; D033921:Vesicular Transport Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3