Epha3 acts as proangiogenic factor in multiple myeloma
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Antonella Caivano1, Francesco La Rocca1, Ilaria Laurenzana1, Tiziana Annese2, Roberto Tamma2, Ubaldo Famigliari3, Vittorio Simeon1, Stefania Trino1, Luciana De Luca1, Oreste Villani4, Simona Berardi5, Antonio Basile5, Angelo Vacca5, Giuseppe Saglio6, Luigi Del Vecchio7,8, Pellegrino Musto9, Daniela Cilloni6
1Laboratory of Pre-clinical and Translational Research, Scientific Institute of Research and Cure (IRCCS), Referral Cancer Center of Basilicata (CROB), Rionero in Vulture, Italy
2Department of Human Anatomy, Histology and Embryology, University of Bari Medical School, Bari, Italy
3Division of Pathology, Department of Oncology, St Luigi Hospital, Turin, Italy
4Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Italy
5Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy
6Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
7CEINGE-Biotecnologie Avanzate s.c.a r.l and Medical Biotechnologies, Federico II University, Naples, Italy
8Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Naples, Italy
9Scientific Direction, IRCCS-CROB, Rionero in Vulture, Italy
Antonella Caivano, email: email@example.com
Keywords: angiogenesis, bone marrow endothelial cells, receptor tyrosine kinase, EphA3, multiple myeloma
Received: September 02, 2016 Accepted: March 01, 2017 Published: March 10, 2017
This study investigates the role of ephrin receptor A3 (EphA3) in the angiogenesis of Multiple Myeloma (MM) and the effects of a selective target of EphA3 by a specific monoclonal antibody on primary bone marrow endothelial cells (ECs) of MM patients.
EphA3 mRNA and protein were evaluated in ECs of MM patients (MMECs), in ECs of patients with monoclonal gammopathies of undetermined significance (MGECs) and in ECs of healthy subjects (control ECs). The effects of EphA3 targeting by mRNA silencing (siRNA) or by the anti EphA3 antibody on the angiogenesis were evaluated. We found that EphA3 is highly expressed in MMECs compared to the other EC types. Loss of function of EphA3 by siRNA significantly inhibited the ability of MMECs to adhere to fibronectin, to migrate and to form tube like structures in vitro, without affecting cell proliferation or viability. In addition, gene expression profiling showed that knockdown of EphA3 down modulated some molecules that regulate adhesion, migration and invasion processes. Interestingly, EphA3 targeting by an anti EphA3 antibody reduced all the MMEC angiogenesis-related functions in vitro. In conclusion, our findings suggest that EphA3 plays an important role in MM angiogenesis.
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