Evidence that tenascin and thrombospondin-1 modulate sprouting of endothelial cells.
AffiliationCRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.
MetadataShow full item record
AbstractCultured endothelial cells undergo a reversible transition from a resting (cobblestone) phenotype to an angiogenic (sprouting) phenotype. This transition mimics the early events of angiogenesis. We have previously reported that the addition of exogenous xylosides inhibits endothelial cel sprouting and modifies the extracellular matrix (ECM) synthesised by the cells. We have now investigated whether endothelial sprouting is mediated by the nature of the extracellular matrix in contact with the cells. Accordingly, cell-free matrices deposited by bovine aortic endothelial cells (BAEC) were isolated. These matrices were produced under conditions in which the formation of the sprouting phenotype was permitted (controls) or inhibited (by the addition of exogenous xylosides). BAEC were then plated on these matrices and grown under conditions which promote sprouting. Sprouting proceeded normally on control matrices, whereas it was inhibited when the cells were grown on matrices deposited in the presence of xylosides. The composition of the permissive and inhibitory matrices was then analysed. Inhibitory matrices contained reduced levels of tenascin and increased levels of thrombospondin-1 by comparison to the permissive matrices. In contrast, no differences were detected in the relative levels of laminin. The roles of tenascin and thrombospondin-1 in endothelial sprouting were confirmed using specific antibodies. Immunolocalisation studies revealed the presence of both proteins in sprouting cells. Antibodies to tenascin inhibited the formation of sprouting cells on permissive matrices and on gelatin-coated dishes without affecting cell growth. Tenascin synthesis was increased when sprouting cells were present in the cultures. Antibodies to thrombospondin-1 stimulated sprouting on inhibitory matrices. These results suggest that the transition from a resting to a sprouting phenotype is promoted by tenascin and inhibited by thrombospondin-1.
CitationEvidence that tenascin and thrombospondin-1 modulate sprouting of endothelial cells. 1995, 108 ( Pt 2):797-809 J. Cell. Sci.
JournalJournal of Cell Science
- Heterogeneity in collagen biosynthesis by sprouting retinal endothelial cells.
- Authors: Canfield AE, Schor AM
- Issue date: 1994 Apr
- The response of endothelial cells to TGF beta-1 is dependent upon cell shape, proliferative state and the nature of the substratum.
- Authors: Sutton AB, Canfield AE, Schor SL, Grant ME, Schor AM
- Issue date: 1991 Aug
- Comparison of normal and tumorigenic endothelial cells: differences in thrombospondin production and responses to transforming growth factor-beta.
- Authors: RayChaudhury A, Frazier WA, D'Amore PA
- Issue date: 1994 Jan
- The in situ localization of tenascin splice variants and thrombospondin 2 mRNA in the avian embryo.
- Authors: Tucker RP
- Issue date: 1993 Jan
- Endothelial cell attachment and spreading on human tenascin is mediated by alpha 2 beta 1 and alpha v beta 3 integrins.
- Authors: Sriramarao P, Mendler M, Bourdon MA
- Issue date: 1993 Aug