Abstract
Mast cells (MCs) are tissue-resident immune cells that are important players in diseases associated with chronic inflammation such as cancer. Since MCs can infiltrate solid tumors and promote or limit tumor growth, a possible polarization of MCs to pro-tumoral or anti-tumoral phenotypes has been proposed and remains as a challenging research field. Here, we review the recent evidence regarding the complex relationship between MCs and tumor cells. In particular, we consider: (1) the multifaceted role of MCs on tumor growth suggested by histological analysis of tumor biopsies and studies performed in MC-deficient animal models; (2) the signaling pathways triggered by tumor-derived chemotactic mediators and bioactive lipids that promote MC migration and modulate their function inside tumors; (3) the possible phenotypic changes on MCs triggered by prevalent conditions in the tumor microenvironment (TME) such as hypoxia; (4) the signaling pathways that specifically lead to the production of angiogenic factors, mainly VEGF; and (5) the possible role of MCs on tumor fibrosis and metastasis. Finally, we discuss the novel literature on the molecular mechanisms potentially related to phenotypic changes that MCs undergo into the TME and some therapeutic strategies targeting MC activation to limit tumor growth.
Highlights
The immune system is composed of white blood cells, organs, and tissues of the lymphatic system, and diverse molecules such as antibodies, enzymes, and cytokines
We will discuss some of the main aspects of the relationship between Mast cells (MCs) and tumors, focusing on the mediators and signaling pathways involved in the chemical communication between tumor cells and MCs that lead to MC recruitment, their effects on angiogenesis, and other intratumoral processes that lead to tumor growth and, the application of that knowledge to the design of MC-directed therapeutic strategies to control cancer development
Animals could not be reconstituted with bone marrow-derived MCs (BMMCs) from WT mice, but MCs could be restored after injection of Stem Cell Factor (SCF) [65,80,81]
Summary
The immune system is composed of white blood cells, organs, and tissues of the lymphatic system, and diverse molecules such as antibodies, enzymes, and cytokines. Research showing that malignant tumors can develop in patients with an apparent functional immune system indicates that immunosurveillance is not sufficient to explain the complex relationship between the immune system and malignant tumors. Those results gave rise to the postulation of a more complex and adequate term known as cancer immunoediting, a dynamic process that occurs in the development of tumors [5]. Innate immune cells, such as macrophages, antigen-presenting dendritic cells, or mast cells have been associated with both pro-and anti-tumoral responses Those findings have opened up new insights regarding therapeutics against cancer. We will discuss some of the main aspects of the relationship between MCs and tumors, focusing on the mediators and signaling pathways involved in the chemical communication between tumor cells and MCs that lead to MC recruitment, their effects on angiogenesis, and other intratumoral processes that lead to tumor growth and, the application of that knowledge to the design of MC-directed therapeutic strategies to control cancer development
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