Plasticity of blood- and lymphatic endothelial cells and marker identification.
The distinction between lymphatic and blood vessels is biologically fundamental. Here we wanted to rigorously analyze the universal applicability of vascular markers and characteristics of the two widely used vascular model systems human microvascular endothelial cell line-1 (HMEC-1) and telomerase-immortalized microvascular endothelial cell line (TIME). Therefore we studied the protein expression and functional properties of the endothelial cell lines HMEC-1 and TIME by flow cytometry and in vitro flow assays. We then performed microarray analyses of the gene expression in these two cell lines and compared them to primary endothelial cells. Using bioinformatics we then defined 39 new, more universal, endothelial-type specific markers from 47 primary endothelial microarray datasets and validated them using immunohistochemistry with normal and pathological tissues. We surprisingly found that both HMEC-1 and TIME are hybrid blood- and lymphatic cells. In addition, we discovered great discrepancies in the previous identifications of blood- and lymphatic endothelium-specific genes. Hence we identified and validated new, universally applicable vascular markers. Summarizing, the hybrid blood-lymphatic endothelial phenotype of HMEC-1 and TIME is indicative of plasticity in the gene expression of immortalized endothelial cell lines. Moreover, we identified new, stable, vessel-type specific markers for blood- and lymphatic endothelium, useful for basic research and clinical diagnostics.
MediCity Research Laboratory, University of Turku, Turku, Finland ; Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland ; Turku Doctoral Program of Biomedical Sciences, Turku, Finland.
Johannes
J
Keuschnigg
Sirkku
S
Karinen
Kaisa
K
Auvinen
Heikki
H
Irjala
John-Patrick
JP
Mpindi
Olli
O
Kallioniemi
Sampsa
S
Hautaniemi
Sirpa
S
Jalkanen
Marko
M
Salmi
D015415:Biomarkers / Q000378:metabolism*; D001773:Blood Cells / Q000166:cytology / Q000378:metabolism*; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D037222:Collectins / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D033081:Shear Strength
D015415:Biomarkers; D051929:CD146 Antigen; C422442:COLEC12 protein, human; D037222:Collectins; C497902:MCAM protein, human; D051116:Receptors, Scavenger