Inhibition of in vivo tumour growth by the blocking of host alpha(v)beta3 and alphaII(b)beta3 integrins.
BACKGROUND
The alpha(v)beta3 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 alphaII(b)beta3 (GPIIb/IIIa) integrin is responsible for platelet activation and, with concomitant release of different stored proangiogenic factors, and tumour cell-platelet interactions.


METHODS
An immunodeficient nude rat model was used to study tumour growth in tibial bone, with tumour cells negative for the target alpha(v)beta3 and alphaII(b)beta3 integrins.


RESULTS
Daily intraperitoneal injections of m7E3 F(ab')2 antibody fragment, blocking human and rat alpha(v)beta3 and alphaII(b)beta3 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.


CONCLUSIONS
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.
Engebraaten
Olav
O
Department of Tumour Biology, Institute for Cancer Research, University of Oslo, Faculty Division, The Norwegian Radium Hospital, Montebello, Oslo, Norway. olav.engebraten@medisin.uio.no
Trikha
Mohit
M
Juell
Siri
S
Garman-Vik
Solveig
S
Fodstad
Øystein
Ø