Targeting vasculogenesis to prevent progression in multiple myeloma

M. Moschetta, Y. Mishima, Y. Kawano, S. Manier, B. Paiva, L. Palomera, Y. Aljawai, A. Calcinotto, C. Unitt, I. Sahin, A. Sacco, S. Glavey, J. Shi, M. R. Reagan, F. Prosper, M. Bellone, Marta Chesi, Peter Leif Bergsagel, A. Vacca, A. M. RoccaroI. M. Ghobrial

Research output: Contribution to journalArticle

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Abstract

The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective ID1+/-ID3-/-mice, we found that MM tumor progression is dependent on EPC trafficking. By performing RNA-sequencing studies, we confirmed that endothelial cells can enhance proliferation and favor cell-cycle progression only in MM clones that are smoldering-like and have dependency on endothelial cells for tumor growth. We further confirmed that angiogenic dependency occurs early and not late during tumor progression in MM. By using a VEGFR2 antibody with anti-vasculogenic activity, we demonstrated that early targeting of EPCs delays tumor progression, while using the same agent at late stages of tumor progression is ineffective. Thus, although there is significant angiogenesis in myeloma, the dependency of the tumor cells on EPCs and vasculogenesis may actually precede this step. Manipulating vasculogenesis at an early stage of disease may be examined in clinical trials in patients with smoldering MM, and other hematological malignancies with precursor conditions.

Original languageEnglish (US)
Pages (from-to)1103-1115
Number of pages13
JournalLeukemia
Volume30
Issue number5
DOIs
StatePublished - May 1 2016

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Multiple Myeloma
Neoplasms
Hematologic Neoplasms
Endothelial Cells
RNA Sequence Analysis
Bone Marrow Cells
Anti-Idiotypic Antibodies
Cell Cycle
Clone Cells
Bone Marrow
Clinical Trials
Growth
erucylphosphocholine
Endothelial Progenitor Cells

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Moschetta, M., Mishima, Y., Kawano, Y., Manier, S., Paiva, B., Palomera, L., ... Ghobrial, I. M. (2016). Targeting vasculogenesis to prevent progression in multiple myeloma. Leukemia, 30(5), 1103-1115. https://doi.org/10.1038/leu.2016.3

Targeting vasculogenesis to prevent progression in multiple myeloma. / Moschetta, M.; Mishima, Y.; Kawano, Y.; Manier, S.; Paiva, B.; Palomera, L.; Aljawai, Y.; Calcinotto, A.; Unitt, C.; Sahin, I.; Sacco, A.; Glavey, S.; Shi, J.; Reagan, M. R.; Prosper, F.; Bellone, M.; Chesi, Marta; Bergsagel, Peter Leif; Vacca, A.; Roccaro, A. M.; Ghobrial, I. M.

In: Leukemia, Vol. 30, No. 5, 01.05.2016, p. 1103-1115.

Research output: Contribution to journalArticle

Moschetta, M, Mishima, Y, Kawano, Y, Manier, S, Paiva, B, Palomera, L, Aljawai, Y, Calcinotto, A, Unitt, C, Sahin, I, Sacco, A, Glavey, S, Shi, J, Reagan, MR, Prosper, F, Bellone, M, Chesi, M, Bergsagel, PL, Vacca, A, Roccaro, AM & Ghobrial, IM 2016, 'Targeting vasculogenesis to prevent progression in multiple myeloma', Leukemia, vol. 30, no. 5, pp. 1103-1115. https://doi.org/10.1038/leu.2016.3
Moschetta M, Mishima Y, Kawano Y, Manier S, Paiva B, Palomera L et al. Targeting vasculogenesis to prevent progression in multiple myeloma. Leukemia. 2016 May 1;30(5):1103-1115. https://doi.org/10.1038/leu.2016.3
Moschetta, M. ; Mishima, Y. ; Kawano, Y. ; Manier, S. ; Paiva, B. ; Palomera, L. ; Aljawai, Y. ; Calcinotto, A. ; Unitt, C. ; Sahin, I. ; Sacco, A. ; Glavey, S. ; Shi, J. ; Reagan, M. R. ; Prosper, F. ; Bellone, M. ; Chesi, Marta ; Bergsagel, Peter Leif ; Vacca, A. ; Roccaro, A. M. ; Ghobrial, I. M. / Targeting vasculogenesis to prevent progression in multiple myeloma. In: Leukemia. 2016 ; Vol. 30, No. 5. pp. 1103-1115.
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