The fibrinogen globe of tenascin-C promotes basic fibroblast growth factor-induced endothelial cell elongation.
To investigate the potential role of tenascin-C (TN-C) on endothelial sprouting we used bovine aortic endothelial cells (BAECs) as an in vitro model of angiogenesis. We found that TN-C is specifically expressed by sprouting and cord-forming BAECs but not by nonsprouting BAECs. To test whether TN-C alone or in combination with basic fibroblast growth factor (bFGF) can enhance endothelial sprouting or cord formation, we used BAECs that normally do not sprout and, fittingly, do not express TN-C. In the presence of bFGF, exogenous TN-C but not fibronectin induced an elongated phenotype in nonsprouting BAECs. This phenotype was due to altered actin cytoskeleton organization. The fibrinogen globe of the TN-C molecule was the active domain promoting the elongated phenotype in response to bFGF. Furthermore, we found that the fibrinogen globe was responsible for reduced cell adhesion of BAECs on TN-C substrates. We conclude that bFGF-stimulated endothelial cells can be switched to a sprouting phenotype by the decreased adhesive strength of TN-C, mediated by the fibrinogen globe.
Schenk
S
S
Department of Research, University Hospital Basel, 4031 Basel, Switzerland.
Chiquet-Ehrismann
R
R
Battegay
E J
EJ
D017398:Alternative Splicing; D000818:Animals; D001011:Aorta; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002642:Chick Embryo; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts; D005898:Glass; D006801:Humans; D008970:Molecular Weight; D018919:Neovascularization, Physiologic; D010969:Plastics; D017384:Sequence Deletion; D019063:Tenascin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
D010969:Plastics; D019063:Tenascin; D016222:Fibroblast Growth Factor 2; D005340:Fibrinogen