Effects of Kaposi's sarcoma-associated herpesvirus ORF K1 on differentiating endothelium in murine embryoid bodies and teratomas.
Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is a prerequisite for Kaposi's sarcoma, a multicentric endothelial tumor of mixed blood vessel-lymphatic phenotype with a marked production of endothelial basement membrane proteins. The viral K1 gene encodes a unique transmembrane protein capable of transforming T lymphocytes experimentally. We studied the effects of K1 regulated by the endothelium-specific tie-1 promoter in the embryonic stem cell (ES)-derived endothelium of subcutaneous murine teratomas and in embryoid body cultures with and without supplemental basic fibroblast growth factor and vascular endothelial growth factor. K1 embryoid bodies showed no difference in endothelial BM protein expression, formation of basal lamina by electron microscopy or fractional area of endothelial growth in comparison with vector controls, but maturation into branching pseudovascular tubes was mildly impaired. Moreover, the marked increase in endothelial fraction induced by both growth factors in the early growth period was absent in K1 clones. Teratoma endothelium, which is partly derived from ES, showed increased proliferation and apoptosis in K1 tumors, coinciding with a possible increased tendency for microhemorrhages. K1 can thus modulate endothelial cell turnover and growth factor response, but does not alter the extracellular matrix of differentiating endothelial cells.
Mebrahtu
Sofia
S
Department of Pathology, Lund University Hospital, Lund, Sweden.
Eriksson
Ulf
U
Rauch
Uwe
U
Warenholt
Janina
J
Bendsöe
Niels
N
Dictor
Michael
M
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D011401:Promoter Regions, Genetic / Q000235:genetics; D042810:Receptor, TIE-1 / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013724:Teratoma; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
C111600:K1 protein, Human herpesvirus 8; D042461:Vascular Endothelial Growth Factor A; D014764:Viral Proteins; D005346:Fibroblast Growth Factors; D042810:Receptor, TIE-1