Abstract |
Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34(+) hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors ( imatinib, masitinib) and tryptase inhibitors ( gabexate and nafamostat mesylate) with the aim to prevent CRC progression.
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Authors | Ilaria Marech, Michele Ammendola, Claudia Gadaleta, Nicola Zizzo, Caroline Oakley, Cosmo Damiano Gadaleta, Girolamo Ranieri |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 20
Issue 27
Pg. 8910-20
(Jul 21 2014)
ISSN: 2219-2840 [Electronic] United States |
PMID | 25083063
(Publication Type: Journal Article, Review)
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Chemical References |
- Angiogenesis Inhibitors
- Angiogenic Proteins
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Topics |
- Angiogenesis Inhibitors
(therapeutic use)
- Angiogenic Proteins
(antagonists & inhibitors, metabolism)
- Animals
- Colorectal Neoplasms
(blood supply, drug therapy, immunology, metabolism, pathology)
- Drug Design
- Humans
- Mast Cells
(drug effects, immunology, metabolism, pathology)
- Molecular Targeted Therapy
- Neovascularization, Pathologic
- Prognosis
- Signal Transduction
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