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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3964-3969
Hepatocyte growth factor-stimulated invasiveness of
monocytes
Mario Beilmann,
George F. Vande Woude,
Hans-Peter Dienes, and
Peter Schirmacher
From the Institute of Pathology, University of Cologne, Cologne,
Germany; and the Division of Basic Sciences, National Cancer Institute,
Frederick Cancer Research and Development Center, Frederick, MD.
Hepatocyte growth factor (HGF) is a pluripotent cytokine
with mitogenic, motogenic, and morphogenic activity for mainly
epithelial and endothelial target cells. We previously demonstrated
that the specific HGF receptor, MET, is induced in stimulated
peripheral blood monocytes. In this study, we analyzed the functional
consequences of MET activation in primary cultures of peripheral blood
monocytes from healthy donors. After stimulation of
MET-expressing monocytes with recombinant HGF, the gene-expression
profile of peripheral blood mononuclear cells and monocytes was
significantly modulated, especially with regard to genes involved in
cell movement. After stimulation of primary cultured monocytes with
HGF, invasion assays showed a significantly increased matrigel invasion
rate that was completely abolished by neutralizing antibodies to HGF.
The HGF-activated invasiveness and the altered
gene-expression profile suggest a proinflammatory role for HGF
stimulation of monocytes and support the hypothesis that the HGF/MET
signaling system plays an important part in the activation of the
nonspecific cellular inflammatory response.
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