Title: An HGF-MSP chimera disassociates the trophic properties of scatter factors from their pro-invasive activity
Authors: Michieli, P ×
Cavassa, S
Basilico, C
De Luca, A
Mazzone, Max
Asti, C
Chiusaroli, R
Guglielmi, M
Bossu, P
Colotta, F
Caselli, G
Comoglio, PM #
Issue Date: May-2002
Publisher: Nature america inc
Series Title: Nature biotechnology vol:20 issue:5 pages:488-495
Abstract: Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) have an intrinsic dual nature: they are trophic cytokines preventing apoptosis on one side and scatter factors promoting invasion on the other. For therapeutic use, their anti-apoptotic activity must be separated from their pro-invasive activity. To this end, we engineered chimeric factors containing selected functional domains of HGF and/or MSP in different combinations, and tested their biological activity. Here we present a chimeric cytokine derived from the chains of HGF and MSP, named Metron factor 1 for its ability to concomitantly activate the HGF receptor (Met) and the MSP receptor (Ron). We provide evidence that Metron factor 1 prevents apoptosis and stimulates cell proliferation at nanomolar concentrations, but is devoid of any pro-invasive activity. In an in vivo murine model of drug-induced nephrotoxicity, intravenous injection of recombinant Metron factor 1 prevented renal damage and preserved tubular integrity.
ISSN: 1087-0156
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Tumor Inflammation and Angiogenesis (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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