Mast Cell-Targeted Strategies in Cancer Therapy

Abstract

Mast cells (MCs) are cells that originate in the bone marrow from pluripotent CD34+ hematopoietic stem cells. Precursors of MCs migrate through the circulation to their target tissues, completing their maturation process into granulated cells under the influence of several microenvironment growth factors. The most important of these factors is the ligand for the c-Kit receptor (c-Kit-R) namely stem cell factor (SCF), secreted mainly by fibroblasts and endothelial cells (ECs). SCF also regulates development, survival and de novo proliferation of MCs. It has already been demonstrated that gain-of-function mutations of gene c-Kit encoding c-Kit-R result in the development of some tumors. Furthermore, MCs are able also to modulate both innate and adaptive immune response and to express the high-affinity IgE receptor following IgE activation. Among the other IgE-independent MC activation mechanisms, a wide variety of other surface receptors for cytokines, chemokines, immunoglobulins, and complement are also described. Interestingly, MCs can stimulate angiogenesis by releasing of several pro-angiogenic cytokines stored in their cytoplasm. Studies published in the last year suggest that angiogenesis stimulated by MCs may play an important role in tumor growth and progression. Here, we aim to focus several biological features of MCs and to summarize new anti-cancer MC-targeted strategies with potential translation in human clinical trials.

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

“…Based on this background, will be possible to design clinical trials with novel anti-angiogenetic therapies targeting MCs degranulation by mean of c-Kit-R tyrosine kinase inhibitors (e.g., masitinib) or inhibiting tryptase by mean of gabexate mesilate or nafamostat mesilate [58,59,60,61,62,63]. Finally, MCDPT could be evaluated as a possible predictive biomarker able to select patients candidable to novels anti-angiogenic strategies.…”

Mast cell‐neural interactions contribute to pain and itch

“…Several other processes have been recognized including tunneling nanotubes (TNT), physical extension via pseudopodia‐like structures, and extracellular trap formation, which may allow for increased interaction of mast cells with vasculature, nervous system, and immune cells, described in detail below. Therefore, mast cells exhibit extraordinary complexity and contribute to diverse functions . This review will examine the interactions of mast cells with the central and peripheral neural systems, pathophysiological mechanisms, and therapeutic targets to treat pain and pruritus.…”

“…Mast cells that become extremely sensitive can lead to well‐known pathologic condition, allergy, and anaphylaxis. In addition to defense against environmental stimuli, mast cells are also sensitive to the endogenous microenvironment and therefore contribute to many biological and pathological processes including vascular physiology, pain, itch, and cancer . Increasing evidence suggests that mast cells contribute to various pathologies via their interactions with the vasculature and CNS.…”

Mast cells—Good guys with a bad image?

“…In rodents, MCs can be divided into mucosal-type MCs Cpa3, heparin and large amounts of histamine. 33,43,54 Low expression of c-Kit or low availability of SCF can be associated with blood disorders, low pigmentation, or fertility complications. Whereas CTMCs appear red in respond to a safranin staining, MMCs can be recognized by a blue color in respond to an alcian blue staining.…”