TY  - JOUR
A1  - Rao, Luigia
A1  - Giannico, Donato
A1  - Leone, Patrizia
A1  - Solimando, Antonio Giovanni
A1  - Maiorano, Eugenio
A1  - Caporusso, Concetta
A1  - Duda, Loren
A1  - Tamma, Roberto
A1  - Mallamaci, Rosanna
A1  - Susca, Nicola
A1  - Buonavoglia, Alessio
A1  - Da Vià, Matteo Claudio
A1  - Ribatti, Domenico
A1  - De Re, Vallì
A1  - Vacca, Angelo
A1  - Racanelli, Vito
T1  - HB-EGF−EGFR signaling in bone marrow endothelial cells mediates angiogenesis associated with multiple myeloma
T2  - Cancers
N2  - Epidermal growth factor receptor (EGFR) and its ligand heparin-binding EGF-like growth factor (HB-EGF) sustain endothelial cell proliferation and angiogenesis in solid tumors, but little is known about the role of HB-EGF–EGFR signaling in bone marrow angiogenesis and multiple myeloma (MM) progression. We found that bone marrow endothelial cells from patients with MM express high levels of EGFR and HB-EGF, compared with cells from patients with monoclonal gammopathy of undetermined significance, and that overexpressed HB-EGF stimulates EGFR expression in an autocrine loop. We also found that levels of EGFR and HB-EGF parallel MM plasma cell number, and that HB-EGF is a potent inducer of angiogenesis in vitro and in vivo. Moreover, blockade of HB-EGF–EGFR signaling, by an anti-HB-EGF neutralizing antibody or the EGFR inhibitor erlotinib, limited the angiogenic potential of bone marrow endothelial cells and hampered tumor growth in an MM xenograft mouse model. These results identify HB-EGF–EGFR signaling as a potential target of anti-angiogenic therapy, and encourage the clinical investigation of EGFR inhibitors in combination with conventional cytotoxic drugs as a new therapeutic strategy for MM.
KW  - multiple myeloma
KW  - HB-EGF
KW  - EGFR
KW  - bone marrow angiogenesis
KW  - endothelial cells
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/20078
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-200786
SN  - 2072-6694
VL  - 12
IS  - 1
ER  -