The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis

Abstract

An association between mast cells and tumor angiogenesis is known to exist, but the exact role that mast cells play in this process is still unclear. It is thought that the mediators released by mast cells are important in neovascularization. However, it is not known how individual mediators are involved in this process. The major constituents of mast cell secretory granules are the mast cell specific proteases chymase, tryptase, and carboxypeptidase A3. Several previous studies aimed to understand the way in which specific mast cell granule constituents act to induce tumor angiogenesis. A body of evidence indicates that mast cell proteases are the pivotal players in inducing tumor angiogenesis. In this review, the likely mechanisms by which tryptase and chymase can act directly or indirectly to induce tumor angiogenesis are discussed. Finally, information presented here in this review indicates that mast cell proteases significantly influence angiogenesis thus affecting tumor growth and progression. This also suggests that these proteases could serve as novel therapeutic targets for the treatment of various types of cancer.

Immunohistochemical Assessment of Mast Cells and Small Blood Vessels in Dentigerous Cyst, Odontogenic Keratocyst, and Periapical Cyst

“…MCs play an important role in the angiogenesis by producing numerous factors such ase heparin, VEGF, platelet-activating factor, tryptase, chemotactic mediators, and FGF. 2,8,9 The role of MCs in vasoinductive events has been investigated by many researchers and these cells have been reported to promote angiogenesis in many lesions. [10][11][12] On the other hand, MCs may suppress the growth of the lesions by synthesizing various factors e.g.…”

The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients

“…Several somatic mutations of c- kit have been implicated in various malignancies, including mastocytosis [10]. Upon activation, MCs can release a plethora of mediators, which includes: preformed mediators stored in their cytoplasmic granules, such as histamine, tryptase and other proteases, cytokines [tumor necrosis factor-α (TNF-α), fibroblast growth factor (FGF), IL-4 and SCF] and proteoglycans (heparin, chondroitin sulfates) [10,15]; neoformed or lipid mediators, products of phospholipase A 2 activation, such as prostaglandins, leukotrienes and platelet-activating factor [4,10,16], and neosynthesized mediators, produced and released upon transcriptional activation, such as IL-1, IL-5, IL-6, IL-8, IL-9, IL-13, IL-17, TNF-α, transforming growth factor-β, FGF and vascular endothelial growth factor (VEGF) [4,10,17,18,19]. …”

“…It has been postulated that the initial stimulus for their accumulation in malignant infiltration areas, typically around blood vessels, originates from malignant cells, and their presence is part of the initial host response to malignancy [4,8]. Among attractants, SCF, c- kit receptor, FGF-2, VEGF and platelet-derived growth factor are major mediators; there is a consequent release from MCs of inflammatory mediators, participating in tissue remodeling and immune suppression.…”

“…Among attractants, SCF, c- kit receptor, FGF-2, VEGF and platelet-derived growth factor are major mediators; there is a consequent release from MCs of inflammatory mediators, participating in tissue remodeling and immune suppression. By these means, MCs participate in tumor progression by realizing proangiogenic and mitogenic factors, suppressing immune surveillance and degrading the extracellular matrix (ECM) [4,8,20]. …”

“…Among them, mast cells (MCs) are accumulated in the BM microenvironment as a host response, displaying potential tumoricidal activity: myeloma cells secrete attractant mediators for MCs, but in turn they secrete several other factors involving MM growth. By these means, MC accumulation, although initially with antitumor potential, supports the dissemination of the disease [3,4]. We have already described that BM MC density (MCD) is correlated with International Staging System stages [5] and moreover with the proliferation rate of myeloma plasma cells [6].…”