Inhibition of the alpha-ν integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo

Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The α v -integrins (α v β 3 , α v β 5 ) mediate the contact of activated endothelial cells to proteins of the extracellular matrix during tumour angiogenesis as a prerequisite for survival of endothelial cells....

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Bibliographic Details
Published in:British journal of cancer 2002-03, Vol.86 (5), p.788-795
Main Authors: Buerkle, M A, Pahernik, S A, Sutter, A, Jonczyk, A, Messmer, K, Dellian, M
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - pharmacology
Antineoplastic Agents - pharmacology
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cricetinae
Drug Resistance
Endothelium - cytology
Endothelium - pathology
Epidemiology
Experimental Therapeutics
Infusions, Parenteral
Integrin alpha1
Leukocytes - immunology
Male
Melanoma - pathology
Microcirculation
Molecular Medicine
Neoplasm Metastasis
Neoplasms, Experimental
Neovascularization, Pathologic
Oligopeptides - pharmacology
Oncology
Skin Neoplasms - pathology
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Summary:Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The α v -integrins (α v β 3 , α v β 5 ) mediate the contact of activated endothelial cells to proteins of the extracellular matrix during tumour angiogenesis as a prerequisite for survival of endothelial cells. The aim of this study was to investigate the effects of application of a methylated cyclic RGD-peptide as an α v -integrin antagonist on angiogenesis, microcirculation, growth and metastasis formation of a solid tumour in vivo . Experiments were performed in the dorsal skinfold preparation of Syrian Golden hamsters bearing the amelanotic hamster melanoma A-Mel-3. Animals were injected intraperitoneally with a methylated cyclic RGD-peptide every 12 h, the control group received an inactive peptide. Microcirculatory parameters of tumour angiogenesis including functional vessel density, red blood cell velocity, vessel diameter and leucocyte–endothelium interaction were analysed using intravital microscopy. In an additional study the effects on growth and metastasis of subcutaneous A-Mel-3 were quantified. Functional vessel density was markedly reduced on day 3 in treated animals compared to controls (37.2±12.1 vs 105.2±11.2 cm −1 ; mean±s.e.m.; P
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6600141