@article{RaoGiannicoLeoneetal.2020,
  author    = {Rao, Luigia and Giannico, Donato and Leone, Patrizia and Solimando, Antonio Giovanni and Maiorano, Eugenio and Caporusso, Concetta and Duda, Loren and Tamma, Roberto and Mallamaci, Rosanna and Susca, Nicola and Buonavoglia, Alessio and Da Vi{\`a}, Matteo Claudio and Ribatti, Domenico and De Re, Vall{\`i} and Vacca, Angelo and Racanelli, Vito},
  title     = {HB-EGF-EGFR signaling in bone marrow endothelial cells mediates angiogenesis associated with multiple myeloma},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {1},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12010173},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200786},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}