Possible biological and translational significance of mast cells density in colorectal cancer

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 27; pp. 8910 - 8920
• Main Authors: Marech, Ilaria, Ammendola, Michele, Gadaleta, Claudia, Zizzo, Nicola, Oakley, Caroline, Gadaleta, Cosmo Damiano, Ranieri, Girolamo
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21.07.2014
• Subjects: Angiogenesis Inhibitors - therapeutic use; Angiogenic Proteins - antagonists & inhibitors; Angiogenic Proteins - metabolism; Animals; cell; Colorectal Neoplasms - blood supply; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - immunology; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; density; Drug Design; Humans; Mast; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Mast Cells - pathology; Molecular Targeted Therapy; Neovascularization, Pathologic; Prognosis; Proteinase-activated; Signal Transduction; Topic Highlight; Tryptase; Angiogenesis; Mast cell density; Proteinase-activated receptor-2; Tryptase inhibitors; Colorectal cancer; Tryptase; Tumor progression; c-Kit receptor tyrosine kinase inhibitors; c-Kit receptor; Vascular endothelial growth factor
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i27.8910

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.