Kumar S, Witzig TE, Timm M, Haug J, Wellik L, Kimlinger TK et al.. Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 104: 1159-1165

Division of Hematology and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Blood (Impact Factor: 10.43). 09/2004; 104(4):1159-65. DOI: 10.1182/blood-2003-11-3811
Source: PubMed

ABSTRACT We compared the angiogenic potential of bone marrow plasma and the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors on plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma (NMM). Cytokine and cytokine-receptor expression was studied by bone marrow immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (RT-PCR) on sorted plasma cells, and quantitative Western blot analysis. Bone marrow angiogenic potential was studied using a human in vitro angiogenesis assay. The expression levels of VEGF, bFGF, and their receptors were similar among MGUS, SMM, and NMM. Sixty-one percent of NMM samples stimulated angiogenesis in the in vitro angiogenesis assay compared with SMM (0%) and MGUS (7%) (P <.001). Importantly, 63% of MGUS samples inhibited angiogenesis compared with SMM (43%) and NMM (4%) (P <.001). The inhibitory activity was heat stable, not overcome by the addition of VEGF, and corresponded to a molecular weight below 10 kd by size-exclusion chromatography. Our results suggest that increasing angiogenesis from MGUS to NMM is, at least in part, explained by increasing tumor burden rather than increased expression of VEGF/bFGF by individual plasma cells. The active inhibition of angiogenesis in MGUS is lost with progression, and the angiogenic switch from MGUS to NMM may involve a loss of inhibitory activity.

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Available from: Shaji K Kumar, Dec 12, 2014
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    • ", though the expression levels of VEGF, bFGF, and their receptors were similar among MGUS, smoldering MM, and newly diagnosed MM [87] "
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    • "We used the in vitro human angiogenesis kit Angiokit for evaluating the anti-angiogenic activity of sorafenib (Kumar et al., 2004b). In the test wells, 10 μl of BM plasma, made cell free by centrifugation was used. "
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    • "EC-like macrophages and apparently typical macrophages contributed sizably to form the neovessel wall in patients with active MM, whereas their vascular supply was minimal in nonactive MM, and absent in MGUS and control patients. Overall data suggest that in active MM, macrophages contribute to neovascularization through a vasculogenic pathway, and that in nonactive MM and MGUS they are prone to behave accordingly, marching in step with progression, hence with the vascular switch (Kumar et al., 2004). "
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