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

World Journal of Gastroenterology 2014年第27期20卷 8910-8920页

作者： Ilaria Marech Michele Ammendola Claudia Gadaleta Nicola Zizzo Caroline Oakley Cosmo Damiano Gadaleta Girolamo Ranieri Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre Istituto Tumori "Giovanni Paolo Ⅱ" 70124 BariItaly Department of Clinical Surgery University of Catanzaro "Magna Graecia" Medical School 88100 Catanzaro Italy Department of Pathology Veterinary Medical School University of Bari Valenzano 70010 Bari Italy

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.

关键词： Tryptase Mast cell density proteinase-activated receptor-2 c-Kit receptor Vascular endothelial growth factor Angiogenesis Colorectal cancer Tumor progression Tryptase inhibitors c-Kit receptor tyrosine kinase inhibitors

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