Title

Targeting vasculogenesis to prevent progression in multiple myeloma.

Document Type

Article

Publication Date

5-1-2016

Institution/Department

Maine Medical Center Research Institute

Journal Title

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

MeSH Headings

Animals, Antibodies, Bone Marrow, Cell Movement, Clone Cells, Disease Progression, Endothelial Cells, Mice, Multiple Myeloma, Neovascularization, Pathologic, Secondary Prevention, Vascular Endothelial Growth Factor Receptor-2

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.

ISSN

1476-5551

First Page

1103

Last Page

1115

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