RT Journal Article
SR Electronic
T1 Inhibition of In Vivo Tumour Growth by the Blocking of Host αvβ3 and αIIbβ3 Integrins
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 131
OP 137
VO 29
IS 1
A1 OLAV ENGEBRAATEN
A1 MOHIT TRIKHA
A1 SIRI JUELL
A1 SOLVEIG GARMAN-VIK
A1 ØYSTEIN FODSTAD
YR 2009
UL http://ar.iiarjournals.org/content/29/1/131.abstract
AB Background: The αvβ3 integrin in the endothelial cell membrane is important for the growth and migration of capillaries into tumour tissue and is also a survival factor for these cells. The αIIbβ3 (GPIIb/IIIa) integrin is responsible for platelet activation and, with concomitant release of different stored proangiogenic factors, and tumour cell-platelet interactions. Materials and Methods: An immunodeficient nude rat model was used to study tumour growth in tibial bone, with tumour cells negative for the target αvβ3 and αIIbβ3 integrins. Results: Daily intraperitoneal injections of m7E3 F(ab')2 antibody fragment, blocking human and rat αvβ3 and αIIbβ3 integrins, reduced the measured size of the tumours growing in the tibial bone by 35% (p=0.012), and also the microvessel density in these tumours. The concentration of the important proangiogenic factor bFGF was significantly reduced by 41% in the treated tumours. The treatment slightly increased the time to the appearance of the tumour from 22.2 to 24.9 days, indicating a small but significant effect on the early stages of tumour growth and invasion through the bone tissue. Conclusion: Integrin-targeted treatment reduced tumour growth, solely targeting the host angiogenesis. This treatment strategy should be further exploited for use in combination with conventional treatment strategies, or the combined targeting of alternative antiangiogenic pathways. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved