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Rao L, Giannico D, Leone P, et al. HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma. Cancers (Basel). 2020;12(1)doi: 10.3390/cancers12010173.
Rao, L., Giannico, D., Leone, P., Solimando, A. G., Maiorano, E., Caporusso, C., Duda, L., Tamma, R., Mallamaci, R., Susca, N., Buonavoglia, A., Da Vià, M. C., Ribatti, D., De Re, V., Vacca, A., & Racanelli, V. (2020). HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma. Cancers, 12(1), . https://doi.org/10.3390/cancers12010173
Rao, Luigia, et al. "HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma." Cancers vol. 12,1 (2020). doi: https://doi.org/10.3390/cancers12010173
Rao L, Giannico D, Leone P, Solimando AG, Maiorano E, Caporusso C, Duda L, Tamma R, Mallamaci R, Susca N, Buonavoglia A, Da Vià MC, Ribatti D, De Re V, Vacca A, Racanelli V. HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma. Cancers (Basel). 2020 Jan 10;12(1). doi: 10.3390/cancers12010173. PMID: 31936715; PMCID: PMC7017291.
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Cancers (Basel). 2020 Jan 10;12(1). doi: 10.3390/cancers12010173.

HB-EGF-EGFR Signaling in Bone Marrow Endothelial Cells Mediates Angiogenesis Associated with Multiple Myeloma.

Cancers

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

Affiliations

  1. Department of Biomedical Sciences and Human Oncology, Guido Baccelli Unit of Internal Medicine, University of Bari Medical School, 70124 Bari, Italy.
  2. Department of Emergency and Organ Transplantations, Section of Pathological Anatomy, University of Bari Medical School, 70124 Bari, Italy.
  3. Department of Interdisciplinary Medicine, University of Bari Medical School, 70124 Bari, Italy.
  4. Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, 70124 Bari, Italy.
  5. Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70124 Bari, Italy.
  6. Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany.
  7. Bio-Proteomics Facility, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano (PN), Italy.
  8. Vito Racanelli MD, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Policlinico, 11 Piazza G. Cesare, 70124 Bari, Italy.

PMID: 31936715 PMCID: PMC7017291 DOI: 10.3390/cancers12010173

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.

Keywords: EGFR; HB-EGF; bone marrow angiogenesis; endothelial cells; multiple myeloma

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