In vitro and in vivo effects of a cyclic peptide with affinity for the alpha(nu)beta3 integrin in human melanoma cells.
Expression of the integrin alpha(nu)beta3 has been shown to be associated with increasing metastatic potential in malignant melanoma. It also has a functional role on vascular endothelial cells during angiogenesis. The cyclic oligopeptide cRGDfV is known to bind with high affinity to alpha(nu)beta3. We have investigated the cellular effects of cRGDfV on a panel of human melanoma cell lines in vitro and also on the A375 melanoma cell line growing as xenografts in nude mice. cRGDfV is a potent inhibitor of alpha(nu)beta3-mediated cell adhesion, however, we have found no convincing evidence that integrin ligation by cRGDfV induces apoptosis in melanoma cell lines. However, cRGDfV when administered subcutaneously into nude mice did inhibit the growth of A375 melanoma xenografts. Histological examination of the tumours indicated that this effect was primarily one of angiogenesis inhibition. The results suggest that agents which target the alpha(nu)beta3 integrin may have a useful role as anti-angiogenesis agents in clinical oncology, but that they may not exert a direct effect on alphavbeta3-expressing tumour cells.
Allman
R
R
Research Department, Velindre Hospital, Whitchurch, Cardiff, UK.
Cowburn
P
P
Mason
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size; D053938:DNA Fragmentation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000627:therapeutic use*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014183:Transplantation, Heterologous
D016326:Extracellular Matrix Proteins; D016023:Integrins; D009842:Oligopeptides; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D002118:Calcium