Mast Cells as Target in Cancer Therapy

Abstract

A close interaction of cancer cells with their microenvironment is important for their growth and survival. In this respect, the involvement of inflammatory cells in the initiation, promotion and progression of cancer has pointed to new therapeutic opportunities in the treatment of cancer. The main immune cell types implicated in tumor-associated inflammation are macrophages, dendritic cells, lymphocytes, neutrophils, eosinophils and mast cells. Their precise role in intercellular communication, regulation of tumor inflammation, and to what respect this inflammation contributes to tumor development, are not completely understood. Mast cells are key effector cells in allergic diseases, but it has become apparent that they also contribute to other pathologies, including autoimmune diseases and cancer. Activated mast cells can release many pro-angiogenic and tumor growth stimulatory mediators. Increased numbers of mast cells are found in many tumors and it has been shown that the number of tumor infiltrating mast cells correlate with increased intratumoral microvessel density, enhanced tumor growth and tumor invasion, and poor clinical outcome. Therefore, modulating mast cell recruitment, viability, activity, or mediator release patterns at malignant sites can be of importance to control tumor growth. In this review, we will focus on the contribution of mast cells to tumor development and growth and the possibilities to interfere in mast cell activation and proliferation in the therapy of cancer.

Inhibition of Mast Cell-Derived Histamine Decreases Human Cholangiocarcinoma Growth and Differentiation via c-Kit/Stem Cell Factor–Dependent Signaling

“…9 Mast cell presence in the tumor microenvironment guarantees the increased release of inflammatory and protumorigenic factors such as histamine, cytokines, and growth factors that all contribute to increasing tumorigenesis. 33 Here, we have found increased infiltration of mast cells and mast cell markers in human CCA, and in support of our findings a study has shown that the density of mast cells is substantially higher in intrahepatic CCA tissues than in nonmalignant and mast cells found surrounding portal tracts. 34 In pancreatic ductal adenocarcinoma nongranulated mast cell density is substantially higher than in the control group, suggesting that mast cells may promote pancreatic tumor growth, 35 and, in a study that used colorectal cancer, mast cell presence and mast cell marker expression, including c-Kit (all up-regulated), were determined to be potential diagnostic markers for the early detection of colorectal cancer.…”

A Critical Role for Mast Cells and Mast Cell-Derived IL-6 in TLR2-Mediated Inhibition of Tumor Growth

“…Although extensive studies demonstrate a protumorigenic role for mast cells (reviewed in Ref. 16), antitumor actions of mast cells have also been reported. In vitro studies have demonstrated mast cells can mediate direct TNF-mediated tumor cell cytotoxicity (17,18).…”

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

“…They support angiogenesis by expression of proangiogenic factors and by inhibition of ECM remodeling the MCs support tumor spread and metastasis. Tumor-associated mast cells are also regarded as potential therapeutic targets [124][125][126][127][128] and prognostic factor [129][130][131].…”

“…Activated MC located in the TME release angiogenic and tumor growth stimulating factors [124,125,381]. Recent findings indicate that tumor-associated mast cells might represent valuable targets for therapeutic interventions, most notably to kinase inhibitors as c-Kit [128,382].…”