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HB-EGF−EGFR signaling in bone marrow endothelial cells mediates angiogenesis associated with multiple myeloma
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-200786
- 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 EGFREpidermal 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.…
Autor(en): | Luigia Rao, Donato Giannico, Patrizia Leone, Antonio Giovanni Solimando, Eugenio Maiorano, Concetta Caporusso, Loren Duda, Roberto Tamma, Rosanna Mallamaci, Nicola Susca, Alessio Buonavoglia, Matteo Claudio Da Vià, Domenico Ribatti, Vallì De Re, Angelo Vacca, Vito Racanelli |
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URN: | urn:nbn:de:bvb:20-opus-200786 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Medizinische Klinik und Poliklinik II |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cancers |
ISSN: | 2072-6694 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 12 |
Heft / Ausgabe: | 1 |
Aufsatznummer: | 173 |
Originalveröffentlichung / Quelle: | Cancers (2020) 12:1, 173. https://doi.org/10.3390/cancers12010173 |
DOI: | https://doi.org/10.3390/cancers12010173 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | EGFR; HB-EGF; bone marrow angiogenesis; endothelial cells; multiple myeloma |
Datum der Freischaltung: | 19.05.2022 |
Datum der Erstveröffentlichung: | 10.01.2020 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |