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.

Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue

“…Several published studies suggest that an increased mast cell density is associated with increased MVD in different animal and human malignancies, but to this regard, very little data have been published for PDAT [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. In the literature, there are some data about the correlation between MVD, evaluated with anti-CD31, and the survival of resected pancreatic cancer patients, demonstrating that high MVD expression is strongly associated with poorer prognosis [ 59 ].…”

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…Elegant studies have demonstrated that mast cell-derived mediators can play protective roles against several venoms [114,115]. Mast cells and their mediators can be involved in several aspects of tumor initiation and growth [21,39,[69][70][71], presumably through the production of several angiogenic and lymphangiogenic factors [19,20,75]. Systemic mastocytosis is a clonal disease associated with a somatic gain-of-function KIT mutation [56,57,123].…”

“…Antonelli and coworkers, based on their long-lasting experience, comprehensively reviewed the roles of immune and inflammatory cells, cytokines, and chemokines in the thyroid cancer microenvironment [74]. Ribatti and Vacca illustrate the role of bone marrow angiogenesis in the pathogenesis and progression of hematological malignancies [75]. Based on their extensive experience, they discuss the roles played by mast cells in the modulation of angiogenesis in patients with multiple myeloma.…”

Mast Cell Protease 7 Promotes Angiogenesis by Degradation of Integrin Subunits

“…Additionally, an increased number of mast cells has been demonstrated in angiogenesis where they are associated with vascular tumors, a number of hematological and solid lung tumors, as well as cutaneous cancer [82,83,84]. This possible relationship between mast cells and angiogenesis may also be mediated through several proangiogenic factors such as VEGF, FGF-2, PDGF, and interleukin-6 (IL-6) that are also stored in mast cell secretory granules [50,52,57,85,86,87].…”

“…Mast cells often accumulate near blood vessels and it is widely recognized that mast cells are associated with newly formed microvasculature [45,46,47]. Various lines of evidence suggested that secreting mast cells can induce and enhance angiogenesis via multiple, and partially interacting pathways [48,49,50,51]. Several of these studies have shown that some mediators released by mast cells such as heparin, histamine, TNF-α, bFGF, stimulate endothelial cell proliferation, thereby influencing angiogenesis [52,53,54,55,56,57].…”