Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

S. Berardi, A. Caivano, R. Ria, B. Nico, R. Savino, R. Terracciano, G. De Tullio, A. Ferrucci, A. De Luisi, M. Moschetta, G. Mangialardi, I. Catacchio, A. Basile, A. Guarini, A. Zito, P. Ditonno, P. Musto, F. Dammacco, D. Ribatti, A. Vacca

Research output: Contribution to journalArticle

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Abstract

Bone marrow (BM) angiogenesis has an important role in the initiation and progression of multiple myeloma (MM). We looked at novel mechanisms of vessel formation in patients with MM through a comparative proteomic analysis between BM endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients with monoclonal gammopathy of undetermined significance (MGECs) and of subjects with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs: filamin A, vimentin, α-crystallin B and 14-3-3ζ/δ protein, not yet linked to overangiogenic phenotype. These proteins gave a typical distribution in the BM of MM patients and in MMECs versus MGECs, plausibly according to a different functional state. Their expression was enhanced by vascular endothelial growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma cell conditioned medium in step with enhancement of MMEC angiogenesis. Their silencing RNA knockdown affected critical MMEC angiogenesis-related functions, such as spreading, migration and tubular morphogenesis. A gradual stabilization of 14-3-3ζ/δ protein was observed, with transition from normal ECs to MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs and maintenance of the cell overangiogenic phenotype. These proteins were substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and panobinostat. Results suggest that these four proteins could be new targets for the antiangiogenic management of MM patients.

Original languageEnglish
Pages (from-to)2258-2269
Number of pages12
JournalOncogene
Volume31
Issue number18
DOIs
Publication statusPublished - May 3 2012

Fingerprint

Multiple Myeloma
Endothelial Cells
Phenotype
Proteins
14-3-3 Proteins
Therapeutics
Bone Marrow
Filamins
Monoclonal Gammopathy of Undetermined Significance
Crystallins
Hepatocyte Growth Factor
Vimentin
Fibroblast Growth Factor 2
Conditioned Culture Medium
RNA Interference
Plasma Cells
Morphogenesis
Bone Marrow Cells
Proteomics
Vascular Endothelial Growth Factor A

Keywords

  • angiogenesis
  • antiangiogenesis
  • endothelial cells
  • multiple myeloma
  • proteomic analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Berardi, S., Caivano, A., Ria, R., Nico, B., Savino, R., Terracciano, R., ... Vacca, A. (2012). Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets. Oncogene, 31(18), 2258-2269. https://doi.org/10.1038/onc.2011.412

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets. / Berardi, S.; Caivano, A.; Ria, R.; Nico, B.; Savino, R.; Terracciano, R.; De Tullio, G.; Ferrucci, A.; De Luisi, A.; Moschetta, M.; Mangialardi, G.; Catacchio, I.; Basile, A.; Guarini, A.; Zito, A.; Ditonno, P.; Musto, P.; Dammacco, F.; Ribatti, D.; Vacca, A.

In: Oncogene, Vol. 31, No. 18, 03.05.2012, p. 2258-2269.

Research output: Contribution to journalArticle

Berardi, S, Caivano, A, Ria, R, Nico, B, Savino, R, Terracciano, R, De Tullio, G, Ferrucci, A, De Luisi, A, Moschetta, M, Mangialardi, G, Catacchio, I, Basile, A, Guarini, A, Zito, A, Ditonno, P, Musto, P, Dammacco, F, Ribatti, D & Vacca, A 2012, 'Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets', Oncogene, vol. 31, no. 18, pp. 2258-2269. https://doi.org/10.1038/onc.2011.412
Berardi, S. ; Caivano, A. ; Ria, R. ; Nico, B. ; Savino, R. ; Terracciano, R. ; De Tullio, G. ; Ferrucci, A. ; De Luisi, A. ; Moschetta, M. ; Mangialardi, G. ; Catacchio, I. ; Basile, A. ; Guarini, A. ; Zito, A. ; Ditonno, P. ; Musto, P. ; Dammacco, F. ; Ribatti, D. ; Vacca, A. / Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets. In: Oncogene. 2012 ; Vol. 31, No. 18. pp. 2258-2269.
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AU - Mangialardi, G.

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AU - Basile, A.

AU - Guarini, A.

AU - Zito, A.

AU - Ditonno, P.

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AU - Ribatti, D.

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