Inhibition of the alpha-v integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo
In: British journal of cancer, Jg. 86 (2002), Heft 5, S. 788-795
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Zugriff:
Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The αv-integrins (αvβ3, αvβ5) 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 αv-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<0.05) and increased subsequently in both groups. Red blood cell velocity at day 3 was below values of controls (0.026±0.01 vs 0.12±0.03 mm s 1; P<0.05). No differences were observed in vessel diameters and leucocyte-endothelium interaction was almost absent in both groups. Furthermore, growth and metastasis of subcutaneous tumours after administration of the cyclic RGD-peptide was significantly delayed in comparison to controls (P<0.05). Inhibition of αv-integrins by a cyclic RGD-peptide resulted in significant reduction of functional vessel density, retardation of tumour growth and metastasis in vivo. Taken together, these results implicate RGD-peptides as agents which have anti-tumour and anti-metastatic activity in vivo.
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Inhibition of the alpha-v integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo
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Autor/in / Beteiligte Person: | BUERKLE, M. A ; PAHERNIK, S. A ; SUTTER, A ; JONCZYK, A ; MESSMER, K ; DELLIAN, M |
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Zeitschrift: | British journal of cancer, Jg. 86 (2002), Heft 5, S. 788-795 |
Veröffentlichung: | Basingstoke: Nature Publishing Group, 2002 |
Medientyp: | academicJournal |
Umfang: | print, 1 p.1/4 |
ISSN: | 0007-0920 (print) |
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