Mast Cells and Angiogenesis in Human Plasma Cell Malignancies

Abstract

Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.

Keywords: angiogenesis; anti-angiogenesis; mast cells; multiple myeloma; plasmocytoma.

Figure 1

Mast cell counts in comparison with the microvessel area in the bone marrow of patients with active and non-active multiple myeloma (MM) and with monoclonal gammopathy of undetermined significance (MGUS). Significance of the regression analysis was calculated by the Pearson’s (r) test. (Modified from reference [46]).

Figure 2

Interplay between plasma cells and mast cells in inducing angiogenic response in multiple myeloma.

Figure 3

Ultrastructural findings of bone marrow biopsies from patients with active multiple myeloma. In (A), a mast cell with typical electron-dense round granules and in (B), at higher magnification, a cytoplasmic granule with a semilunar aspect (arrow), among other typical round granules, is recognizable. Bars, (A) 0.08 μm; (B) 0.02 μm (Reproduced from reference [46]).

Figure 4

Double FVIII-RA (green) and tryptase (red) confocal laser microscopy from multiple myeloma (MM) (A) and monoclonal gammopathy of undetermined significance (MGUS) (B) bone marrow biopsy specimens. In (A), a MM vessel is lined by both endothelial cells positive for FVIII-RA and by mast cells positive for tryptase (arrowheads). Mast cells containing tryptase-positive granules (arrows) are also recognizable on the abluminal side of the vessel. In (B), a MGUS vessel is lined only by endothelial cells positive for FVIII-RA and is surrounded by tryptase-positive mast cells (arrows). Bars, (A) 15.8 μm; (B) 12.5 μm (Reproduced from reference [77]).