Identification of laminin alpha1 and beta1 chain peptides active for endothelial cell adhesion, tube formation, and aortic sprouting.
Laminin-1 is a basement membrane glycoprotein that promotes several biological activities including cell attachment, tumor metastasis, and angiogenesis. Angiogenesis plays an important role in tissue formation, reproduction, wound healing, and several pathological conditions. In this study, we screened 405 synthetic peptides from the alpha1 and beta1 chains to identify potential sites on laminin-1 active with endothelial cells. Peptides were initially screened by testing both endothelial cell adhesion to peptide-coated wells and tube formation on Matrigel in the presence of soluble peptide. Twenty active peptides were identified in these screens. A secondary screen using the rat aortic ring sprouting assay identified 13 of the 20 peptides that stimulated endothelial sprouting. Several of these active peptides were also found to stimulate human umbilical vein endothelial cell migration in Boyden chamber assays. Differences in the amount of peptide needed for the response and in the resultant morphologies/responses were observed between the peptides in all of the assays. Our results suggest that several active domains on laminin-1 may play important roles in stimulating different steps in angiogenesis.
Malinda
K M
KM
a Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, NIH, Bethesda, Maryland 20892-4370, USA.
Nomizu
M
M
Chung
M
M
Delgado
M
M
Kuratomi
Y
Y
Yamada
Y
Y
Kleinman
H K
HK
Ponce
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007797:Laminin / Q000138:chemical synthesis / Q000502:physiology*; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D007797:Laminin; D010455:Peptides; C084098:laminin A