© 1999 American Heart Association, Inc.
Original Contribution |
Identification of Endothelial Cell Binding Sites on the Laminin 
1 Chain
From the Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Md.
Correspondence to Hynda K. Kleinman, PhD, CDBRB, NIDR, NIH, Bldg 30, Rm 433, Bethesda, MD 20892. E-mail kleinman{at}yoda.nidr.nih.gov
Abstract—The laminins belong to
a family of trimeric basement membrane glycoproteins with
multiple domains, structures, and functions.
Endothelial cells bind laminin-1 and form
capillary-like structures when plated on a laminin-1–rich basement
membrane matrix, Matrigel. Laminin-1 is composed of 3 chains,
1, ß1, and 
1. Because laminin-1 is known to contain multiple
biologically active sites, we have screened 156 synthetic overlapping
peptides spanning the entire laminin 1 chain for potential
angiogenic sequences. Only 7 of these peptides, designated as C16, C25,
C30, C38, C64, C75, and C102, disrupted the formation of capillary-like
structures by human umbilical vein endothelial cells on
Matrigel. Dose-response experiments in the presence of 50 to 200
µg/mL showed that tube formation was prevented by most peptides at
150 and 200 µg/mL, except for C16, which showed strong activity at
all concentrations. Active peptides promoted vessel sprouting from
aorta rings and angiogenesis in the chick chorioallantoic membrane
assay. In addition, the active peptides also promoted
endothelial cell adhesion to dishes coated with 0.1
µg of peptide and inhibited attachment to laminin-1 but not to
plastic or fibronectin. Four of the active peptides, C25, C38, C75, and
C102, may have cell-type specificity with endothelial
cells, since they did not promote PC12 neurite outgrowth or adhesion of
B16-F10 melanoma and human submandibular gland cells. These results
suggest that specific laminin 1–chain peptides have angiogenic
activity with potential therapeutic applications.
Key Words: angiogenesis • laminin • endothelium • extracellular matrix • adhesion
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