HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients

P. Storti, G. Donofrio, S. Colla, I. Airoldi, M. Bolzoni, L. Agnelli, M. Abeltino, K. Todoerti, M. Lazzaretti, C. Mancini, D. Ribatti, S. Bonomini, V. Franceschi, V. Pistoia, G. Lisignoli, A. Pedrazzini, O. Cavicchi, A. Neri, V. Rizzoli, N. Giuliani

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in MM.

Original languageEnglish
Pages (from-to)527-537
Number of pages11
JournalLeukemia
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Multiple Myeloma
Chorioallantoic Membrane
Inbred NOD Mouse
SCID Mice
Homeobox Genes
Angiogenesis Inducing Agents
Fibroblast Growth Factor 2
Microarray Analysis
Plasma Cells
Small Interfering RNA
Genes
Neoplasms
Down-Regulation
Bone Marrow
Cell Line
Polymerase Chain Reaction
Growth

Keywords

  • angiogenesis
  • HOXB7
  • microenvironment
  • multiple myeloma
  • transcription factors

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. / Storti, P.; Donofrio, G.; Colla, S.; Airoldi, I.; Bolzoni, M.; Agnelli, L.; Abeltino, M.; Todoerti, K.; Lazzaretti, M.; Mancini, C.; Ribatti, D.; Bonomini, S.; Franceschi, V.; Pistoia, V.; Lisignoli, G.; Pedrazzini, A.; Cavicchi, O.; Neri, A.; Rizzoli, V.; Giuliani, N.

In: Leukemia, Vol. 25, No. 3, 03.2011, p. 527-537.

Research output: Contribution to journalArticle

Storti, P, Donofrio, G, Colla, S, Airoldi, I, Bolzoni, M, Agnelli, L, Abeltino, M, Todoerti, K, Lazzaretti, M, Mancini, C, Ribatti, D, Bonomini, S, Franceschi, V, Pistoia, V, Lisignoli, G, Pedrazzini, A, Cavicchi, O, Neri, A, Rizzoli, V & Giuliani, N 2011, 'HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients', Leukemia, vol. 25, no. 3, pp. 527-537. https://doi.org/10.1038/leu.2010.270
Storti, P. ; Donofrio, G. ; Colla, S. ; Airoldi, I. ; Bolzoni, M. ; Agnelli, L. ; Abeltino, M. ; Todoerti, K. ; Lazzaretti, M. ; Mancini, C. ; Ribatti, D. ; Bonomini, S. ; Franceschi, V. ; Pistoia, V. ; Lisignoli, G. ; Pedrazzini, A. ; Cavicchi, O. ; Neri, A. ; Rizzoli, V. ; Giuliani, N. / HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. In: Leukemia. 2011 ; Vol. 25, No. 3. pp. 527-537.
@article{0139a5500eaa45beb02f5977b4d66b03,
title = "HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients",
abstract = "The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40{\%} of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in MM.",
keywords = "angiogenesis, HOXB7, microenvironment, multiple myeloma, transcription factors",
author = "P. Storti and G. Donofrio and S. Colla and I. Airoldi and M. Bolzoni and L. Agnelli and M. Abeltino and K. Todoerti and M. Lazzaretti and C. Mancini and D. Ribatti and S. Bonomini and V. Franceschi and V. Pistoia and G. Lisignoli and A. Pedrazzini and O. Cavicchi and A. Neri and V. Rizzoli and N. Giuliani",
year = "2011",
month = "3",
doi = "10.1038/leu.2010.270",
language = "English",
volume = "25",
pages = "527--537",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients

AU - Storti, P.

AU - Donofrio, G.

AU - Colla, S.

AU - Airoldi, I.

AU - Bolzoni, M.

AU - Agnelli, L.

AU - Abeltino, M.

AU - Todoerti, K.

AU - Lazzaretti, M.

AU - Mancini, C.

AU - Ribatti, D.

AU - Bonomini, S.

AU - Franceschi, V.

AU - Pistoia, V.

AU - Lisignoli, G.

AU - Pedrazzini, A.

AU - Cavicchi, O.

AU - Neri, A.

AU - Rizzoli, V.

AU - Giuliani, N.

PY - 2011/3

Y1 - 2011/3

N2 - The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in MM.

AB - The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously associated to tumor progression and angiogenesis; here we investigated the potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM) cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at the diagnosis related to high bone marrow angiogenesis and overexpressed in about 40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7 expression in MM cells by a lentiviral vector significantly modified their transcriptional and angiogenic profile, checked by combined microarray and angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene signature was also validated in a large independent dataset of MM patients. Accordingly, MM-induced vessel formation was significantly increased by HOXB7 overexpression both in vitro angiogenic and chorioallantoic membrane assays, as well as the HOXB7 silencing by small interfering RNA inhibited the production of angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor growth, increased MM-associated angiogenesis and the expression of pro-angiogenic genes by microarray analysis supporting the critical role of HOXB7 in the angiogenic switch in MM.

KW - angiogenesis

KW - HOXB7

KW - microenvironment

KW - multiple myeloma

KW - transcription factors

UR - http://www.scopus.com/inward/record.url?scp=79952371298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952371298&partnerID=8YFLogxK

U2 - 10.1038/leu.2010.270

DO - 10.1038/leu.2010.270

M3 - Article

C2 - 21183939

AN - SCOPUS:79952371298

VL - 25

SP - 527

EP - 537

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 3

ER -