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Modulation of endothelial cell proliferation, adhesion, and motility by recombinant heparin‐binding domain and synthetic peptides from the type I repeats of thrombospondin
Author(s) -
Vogel Tikva,
Guo NengHua,
Krutzsch Henry C.,
Blake Diane A.,
Hartman Jacob,
Mendelovitz Simona,
Panet Amos,
Roberts David D.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240530109
Subject(s) - thrombospondin , angiogenesis , microbiology and biotechnology , endothelial stem cell , thrombospondin 1 , heparin , angiogenesis inhibitor , cell adhesion , biology , biochemistry , chemistry , cell growth , cell , cancer research , in vitro , metalloproteinase , matrix metalloproteinase
Thrombospondin is an inhibitor of angiogenesis that modulates endothelial cell adhesion, proliferation, and motility. Synthetic peptides from the second type I repeat of human thrombospondin containing the consensus sequence ‐Trp‐Ser‐Pro‐Trp‐ and a recombinant heparin binding fragment from the amino‐terminus of thrombospondin mimic several of the activities of the intact protein. The peptides and heparin‐binding domain promote endothelial cell adhesion, inhibit endothelial cell chemotaxis to basic fibroblast growth factor (bFGF), and inhibit mitogenesis and proliferation of aortic and corneal endothelial cells. The peptides also inhibit heparin‐dependent binding of bFGF to corneal endothelial cells. The antiproliferative activities of the peptides correlate with their ability to bind to heparin and to inhibit bFGF binding to heparin. Peptides containing amino acid substitutions that eliminate heparin‐binding do not alter chemotaxis or proliferation of endothelial cells. Inhibition of proliferation by the peptide is time‐dependet and reversible. Thus, the antiproliferative activities of the thrombospondin peptides and recombinant heparin‐binding domain result at least in part from competition with heparin‐dependent growth factors for binding to endothelial cell proteoglycans. These results suggest that both the Trp‐Ser‐Xaa‐Trp sequences in the type I repeats and the amino‐terminal domain play roles in the antiproliferative activity of thrombospondin.