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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1970-1976
NEOPLASIA
Platelet-endothelial interaction in tumor angiogenesis and
microcirculation
Philipp C. Manegold,
Joerg Hutter,
Sascha A. Pahernik,
Konrad Messmer, and
Marc Dellian
From the Institute for Surgical Research and the
Department of Otorhinolaryngology, Klinikum Grosshadern,
Ludwig-Maximilians-University Munich, Munich, Germany; and
the Department of Urology, University of Mainz, Mainz,
Germany.
Activated platelets release angiogenic growth factors and have
therefore been proposed to contribute to tumor angiogenesis within a
potentially prothrombotic tumor microcirculation. The aim of the study
was to investigate interactions of platelets with the angiogenic
microvascular endothelium of highly vascularized solid tumors during
growth and in response to endothelial stimulation in comparison with
normal subcutaneous tissue. Experiments were performed in the dorsal
skinfold chamber preparation of C57BL/6J mice bearing the Lewis lung
carcinoma (LLC-1) or methylcholanthrene-induced fibrosarcoma
(BFS-1). Fluorescently labeled rolling and adherent platelets,
red blood cell velocity, and vessel diameters were assessed by
intravital fluorescence microscopy on days 1, 3, 8, and 14 after tumor
cell implantation. Slightly elevated numbers of rolling platelets were
observed in the early stages of tumor angiogenesis at day 1 (control,
1.7 ± 0.6; LLC-1, 3.4 ± 1.8; BFS-1, 3.0 ± 0.7 [1/mm/s],
P < .05) and day 3 (control, 1.6 ± 0.6; LLC-1, 4.1 ± 1.7, P < .05; BFS-1, 2.3 ± 0.5 [1/mm/s])
after tumor cell implantation. Endothelial stimulation with calcium
ionophore A23187 at day 14 after tumor cell implantation resulted in a
minor increase to 2.1 ± 0.4 (LLC-1) and 1.8 ± 0.8 (BFS-1) rolling
platelets (1/mm/s) in tumor microvessels compared with 4.9 ± 0.9 in
controls (P < .05). Platelet adherence was not observed.
We therefore conclude that in the 2 experimental tumors under study,
(1) slightly increased platelet rolling is a transient phenomenon after
tumor cell implantation, and (2) platelet-endothelial interaction in
response to endothelial stimulation is reduced in tumor microvessels.
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