MURINE EPIDERMAL GROWTH-FACTOR (EGF) FRAGMENT(33-42) INHIBITS BOTH EGF-DEPENDENT AND LAMININ-DEPENDENT ENDOTHELIAL-CELL MOTILITY AND ANGIOGENESIS

Laminin, murine epidermal growth factor (mEGF), and the synthetic lami nin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of mur ine laminin, CDPGYIGSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF(33-42) (a l inear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S- Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic c hick endothelial cells, mEGF(33-42) blocks both EGF- and laminin-stimu lated locomotion of endothelial cells. In vivo, mEGF(33-42) also block s both laminin- and mEGF-induced angiogenesis in the chick, In the hum an cell line, Lam.B1(925-933) has an additive effect in coincubation w ith either laminin or mEGF, but it blocks their effects in the chick c ells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but b locks laminin-induced angiogenesis, Thus, mEGF(33-42) acts as a genera l laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonis t in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF(33-42) may be the source of the antagonistic effects seen wit h this peptide as compared with the laminin fragment. These findings h ave important implications in the design of human antiangiogenic agent s, and also in the use of chick models in the study of human disease.