title: Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.
abstract: Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (mainly tryptase). In fact, in several animal and human malignancies, MCs density is highly correlated with tumor angiogenesis. In particular, tryptase, an agonist of the proteinase-activated receptor-2 (PAR-2), represents one of the most powerful angiogenic mediators released by human MCs after c-Kit receptor activation. This protease, acting on PAR-2 by its proteolytic activity, has angiogenic activity stimulating both human vascular endothelial and tumor cell proliferation in paracrine manner, helping tumor cell invasion and metastasis. Based on literature data it is shown that tryptase may represent a promising target in cancer treatment due to its proangiogenic activity. Here we focused on molecular mechanisms of three tryptase inhibitors (gabexate mesylate, nafamostat mesylate, and tranilast) in order to consider their prospective role in cancer therapy.
authors.affiliation: Department of Medical and Surgery Sciences, Clinical Surgery Unit, University "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ammendola
authors.affiliation: Department of Health Science, Clinical Pharmacology and Pharmacovigilance Unit and Pharmacovigilance's Centre Calabria Region, University of Catanzaro "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Leporini
authors.affiliation: Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, Istituto Tumori "Giovanni Paolo II," Viale Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Marech
authors.affiliation: Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, Istituto Tumori "Giovanni Paolo II," Viale Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Cosmo Damiano
authors.initials: CD
authors.lastname: Gadaleta
authors.affiliation: Radiotherapy Unit, Istituto Tumori "Giovanni Paolo II," Viale Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scognamillo
authors.affiliation: Department of Medical and Surgery Sciences, Clinical Surgery Unit, University "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Sacco
authors.affiliation: Department of Medical and Surgery Sciences, Clinical Surgery Unit, University "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sammarco
authors.affiliation: Department of Health Science, Clinical Pharmacology and Pharmacovigilance Unit and Pharmacovigilance's Centre Calabria Region, University of Catanzaro "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Department of Health Science, Clinical Pharmacology and Pharmacovigilance Unit and Pharmacovigilance's Centre Calabria Region, University of Catanzaro "Magna Graecia" Medical School, Viale Europa, Germaneto, 88100 Catanzaro, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.affiliation: Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, Istituto Tumori "Giovanni Paolo II," Viale Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Ranieri
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D016670:Gabexate / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism; D053802:Tryptases / Q000037:antagonists & inhibitors / Q000235:genetics*; D059016:Tumor Microenvironment / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A
chemical_list: D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D016670:Gabexate; D053802:Tryptases