Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells?
By counteracting the shortening of chromosome telomeres, telomerase reverse transcriptase (hTERT) prevents senescence and age-related cell death. Embryonic cells display a high telomerase activity that declines rapidly with cell differentiation. Conversely, de-differentiated tumor cells tend to re-express telomerase. In view of the controversial data on the reciprocal correlation between cell proliferation and differentiation, we questioned whether telomerase overexpression and the resulting immortalization would affect the functional phenotype of human endothelial cells. Our comparative analysis addressed (1) distinct cell adhesion to different ECM-proteins analyzed on miniaturized multisubstrate arrays (MSA), (2) protein expression of diverse markers, (3) the uptake of DiI-Ac-LDL, (4) the inflammatory response based on upregulation of ICAM-1, (5) tube formation, and (6) the barrier properties of cell monolayers in transfilter cultures. Our results, based on some 40 data sets, demonstrate that immortalization of primary endothelial cells by hTERT maintains the typical endothelial characteristics without any sign of functional de-differentiation.
Baumer
Yvonne
Y
NMI, Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
Funk
Dorothee
D
Schlosshauer
Burkhard
B
D002232:Carbocyanines / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054337:Cell Dedifferentiation; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D010539:Permeability; D011506:Proteins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D002232:Carbocyanines; D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; C024286:3,3'-dioctadecylindocarbocyanine; D007371:Interferon-gamma; C509186:TERT protein, human; D019098:Telomerase