scholarly journals Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 986
Author(s):  
Mark R. Hanes ◽  
Carman A. Giacomantonio ◽  
Jean S. Marshall
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Development ◽  
Breast Cancers ◽  
Diverse Range ◽  
Effector Cells ◽  
Cell Functions ◽  
Cell Responses ◽  
Cancer Settings

Mast cells are important sentinel cells in host defense against infection and major effector cells in allergic disease. The role of these cells in cancer settings has been widely debated. The diverse range of mast cell functions in both immunity and tissue remodeling events, such as angiogenesis, provides multiple opportunities for mast cells to modify the tumor microenvironment. In this review, we consider both skin and breast cancer settings to address the controversy surrounding the importance of mast cells in the host response to tumors. We specifically address the key mediators produced by mast cells which impact tumor development. The role of environmental challenges in modifying mast cell responses and opportunities to modify mast cell responses to enhance anti-tumor immunity are also considered. While the mast cell’s role in many cancer contexts is complicated and poorly understood, the activities of these tissue resident and radioresistant cells can provide important opportunities to enhance anti-cancer responses and limit cancer development.

scholarly journals Fine-tuning Mast Cells is Essential for the Maintenance and Regulation of the Systemic and Immune Homeostasis

2021 ◽  
Vol 10 (2) ◽  
pp. 60
Author(s):  
Sylvia Frisancho-Kiss
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Scientific Literature ◽  
Fine Tuning ◽  
Viral Reservoir ◽  
Evolutionary Perspective ◽  
Cell Functions ◽  
The Past ◽  
Allergies And Asthma

During the past decades, populous expansion in mast cell scientific literature came forth with more, than forty-four thousand PubMed publications available to date. Such surge is due to the appreciation of the momentous role of mast cells in the evolution of species, in the development and maintenance of vital physiological functions, such as reproduction, homeostasis, and fluids, diverse immunological roles, and the potential of far-reaching effects despite minute numbers. While the emerging knowledge of the importance of mast cells in equilibrium comes of age when looking at the matter from an evolutionary perspective, the recognition of mast cells beyond detrimental performance in allergies and asthma, during protection against parasites, falters. Beyond well known classical functions, mast cells can process and present antigens,can serve as a viral reservoir, can respond to hormones and xenobiotics,initiate antiviral and antibacterial responses, phagocytosis, apoptosis, and participate in important developmental cornerstones. During evolution,upon the development of a sophisticated niche of innate and adaptive cell populations, certain mast cell functions became partially transmutable,yet the potency of mast cells remained considerable. Reviewing mast cells enables us to reflect on the certitude, that our sophisticated, complex physiology is rooted deeply in evolution, which we carry ancient remnants of, ones that may have decisive roles in our functioning. This communication sets out the goal of characterizing mast cells, particularly the aspects less in limelight yet of immense significance, without the aspiration exhaust it all.

scholarly journals Role of Mast Cell-Derived Adenosine in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2603 ◽  
Author(s):  
Yaara Gorzalczany ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Inflammatory Mediators ◽  
Adenosine Receptor ◽  
Tumor Development ◽  
A3 Adenosine Receptor

Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs function to promote or restrict tumor growth. By responding to multiple stimuli MCs release multiple inflammatory mediators, that contribute to the resolution of infection and resistance to envenomation, but also have the potency to promote or inhibit malignancy. Thus, MCs seem to possess the power to define tumor projections. Given this remarkable plasticity of MC responsiveness, there is an urgent need of understanding how MCs are activated in the tumor microenvironment (TME). We have recently reported on the direct activation of MCs upon contact with cancer cells by a mechanism involving an autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we summarized the evidence on the role of adenosine signaling in cancer, in MC mediated inflammation and in the MC-cancer crosstalk.

Superior Immunomodulatory Effects of Cultured Mast Cells: Potent Strategy for Treatment of Gvhd

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4684-4684
Author(s):  
Raita Araki ◽  
Hideaki Maeba ◽  
Rie Kuroda ◽  
Toshihiro Fujiki ◽  
Shintaro Mase ◽  
...  
Keyword(s):  
Mast Cells ◽  
Acute Gvhd ◽  
Mixed Lymphocyte Reaction ◽  
Conflicts Of Interest ◽  
Tumor Development ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Effector Cells ◽  
Ige Mediated

Abstract Abstract 4684 Mast cells have long been known as effector cells in the various IgE-mediated allergic responses. However, recent studies demonstrated that mast cells play various roles in immune reactions in coordination with other immune cells. That is, mast cells exert pro-inflammatory or anti-inflammatory effects depending on the situation. In addition, mast cells have association with tumor development. In allogeneic hematopoietic stem cell transplantation (HSCT), only a few have reported that the numbers of mast cells were correlated with the severity of acute GVHD in the skin. However, exact role of mast cells in GVHD remains unclear. With the purpose of potential application of mast cells in a clinical HSCT for GVHD, mixed lymphocyte reaction (MLR) was performed to clarify whether mast cells impaired the alloreaction or not. To generate bone marrow derived cultured mast cells (BMCMCs), BM cells from mice were incubated in complete RPMI containing IL-3 for 6 weeks. As shown in the figure, we showed that MLR was strongly inhibited when BMCMCs from the stimulator strain were added to the coculture (Stimulator (S): DCs obtained from C57BL/6, Responder (R): splenocytes from Balb/c, BMCMCs from C57BL/6). Next, when BMCMCs from the responder strain were added to the coculture, MLR was also suppressed (S: DCs obtained from C57BL/6, R: splenocytes from Balb/c, BMCMCs from Balb/c). In conclusion, mast cells suppressed lymphocyte proliferation induced by allo-DCs in an MHC-independent manner. Just like mesenchymal stem cells, cell therapy utilizing cultured mast cells may reduce GVHD severity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunoglobulin E–dependent Active Fatal Anaphylaxis in Mast Cell–deficient Mice

1998 ◽  
Vol 188 (9) ◽  
pp. 1587-1592 ◽  
Author(s):  
Il Hwan Choi ◽  
Young Min Shin ◽  
Jae Seung Park ◽  
Moo Sam Lee ◽  
Eue Hyeog Han ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Platelet Activating Factor ◽  
Serum Levels ◽  
Effector Cells ◽  
Plasma Histamine Level ◽  
Central Effector ◽  
Fatal Anaphylaxis

Mast cells have long been believed to be the central effector cells in the development of immunoglobulin (Ig)E-dependent anaphylaxis. In this study, we investigated the role of mast cells in IgE-dependent hapten-induced active fatal anaphylaxis using mast cell–deficient WBB6F1- W/Wv (W/Wv) and congenic normal (+/+) mice. Although a 5-min delay in shock signs and death were observed in W/Wv mice, 100% fatal reactions to penicillin V (Pen V) occurred in both +/+ and W/Wv mice. Administration of monoclonal anti–IL-4 antibody completely prevented the fatal reactions, and the effect of anti–IL-4 was associated with its suppressive activity on Pen V–specific serum levels of IgE, but not IgG. The platelet-activating factor (PAF) antagonist, BN 50739, completely prevented the fatal reactions in both strains of mice. Our kinetic study revealed, in contrast to no elevation of plasma histamine level in W/Wv mice, high levels of PAF in the circulation after challenge in both +/+ and W/Wv mice, albeit to a lesser degree in the latter case. These data indicate that cells other than mast cells are sufficient to induce an IgE-dependent active fatal anaphylaxis by elaborating PAF, which is the critical mediator for fatal murine anaphylaxis.

scholarly journals Aldh2 Attenuates Stem Cell Factor/Kit-Dependent Signaling and Activation in Mast Cells

2019 ◽  
Vol 20 (24) ◽  
pp. 6216 ◽  
Author(s):  
Do-Kyun Kim ◽  
Young-Eun Cho ◽  
Byoung-Joon Song ◽  
Toshihiro Kawamoto ◽  
Dean D. Metcalfe ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Oxygen Species ◽  
Cell Reactivity ◽  
Downstream Signaling ◽  
Cell Responses ◽  
Kinase Phosphorylation

Mitochondrial aldehyde dehydrogenase (ALDH2) metabolizes endogenous and exogenous aldehydes and protects cells against oxidative injury. Inactivating genetic polymorphisms in humans are common and associate with alcohol flush reactions. However, whether mast cell Aldh2 activity impacts normal mast cell responses is unknown. Using bone marrow-derived mast cells from Aldh2 knockout mice, we found evidence for a role of mast cell Aldh2 in Kit-mediated responses. Aldh2-deficient mast cells showed enhanced Kit tyrosine kinase phosphorylation and activity after stimulation with its ligand (stem cell factor) and augmentation of downstream signaling pathways, including Stat4, MAPKs, and Akt. The activity of the phosphatase Shp-1, which attenuates Kit activity, was reduced in Aldh2−/− mast cells, along with an increase in reactive oxygen species, known to regulate Shp-1. Reduced Shp-1 activity concomitant with sustained Kit signaling resulted in greater proliferation following Kit engagement, and increased mediator and cytokine release when Aldh2−/− mast cells were co-stimulated via Kit and FcεRI. However, FcεRI-mediated signaling and responses were unaffected. Therefore, our findings reveal a functional role for mast cell intrinsic Aldh2 in the control of Kit activation and Kit-mediated responses, which may lead to a better understanding of mast cell reactivity in conditions related to ALDH2 polymorphisms.

scholarly journals Role of Galectin-3 in Mast Cell Functions: Galectin-3-Deficient Mast Cells Exhibit Impaired Mediator Release and Defective JNK Expression

2006 ◽  
Vol 177 (8) ◽  
pp. 4991-4997 ◽  
Author(s):  
Huan-Yuan Chen ◽  
Bhavya B. Sharma ◽  
Lan Yu ◽  
Riaz Zuberi ◽  
I-Chun Weng ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Mediator Release ◽  
Cell Functions ◽  
Galectin 3

Kinase Suppressor of Ras Plays a Critical Role in Modulating Inflammatory Mast Cell Functions.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2407-2407
Author(s):  
Meng Chen ◽  
Whitney Horn ◽  
Xiaohong Li ◽  
Scott Knowles ◽  
David Ingram ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Western Blots ◽  
Cell Functions ◽  
Kit Ligand ◽  
Fold Reduction ◽  
Kinase Suppressor Of Ras ◽  
And Migration

Abstract The Raf/MEK/extracellular signal-regulated kinase (ERK) kinase cascade and the Ras-PI3-K-Akt pathways are intricately regulated and evolutionarily conserved pathways that have been implicated in specialized cellular functions including proliferation, differentiation, survival and degranulation. Recent data suggest that the strength and duration of these signals is maintained by extracellular growth factors and integrin stimuli as well as intracellular protein scaffolds. In the present study, we investigated the role of Kinase suppressor of Ras (KSR), a scaffold that appears to regulate both Ras-Erk and Ras-PI3-K activity in influencing mast cell function. In vivo, KSR−/− mice have a 2–3 fold reduction of resident mast cells in multiple organs including the peritoneum and the skin as evaluated by scoring Alcian blue positive cells. To evaluate the mechanistic underpinnings of these in vivo observations, bone marrow derived mast cells (BMMCs) were generated and proliferation, survival, degranulation, and migration was examined. A 3–4 fold reduction in kit-ligand mediated proliferation as measured by [3H]thymidine incorporation was observed in KSR−/− BMMCs as compared to WT BMMCs. In addition, a 50% increase in apoptosis was observed in KSR−/− mast cells as compared to that in WT cells as measured by flow cytometeric analysis using Annexin/PI staining. Given that Erk and Akt are established molecular targets control proliferation and survival, respectively; we next performed western blots to evaluate if the changes in biological activity was associated with these signaling pathways. Importantly, a reduction in phosphorylation of ERK and phosphorylation of AKT was observed in the KSR −/− BMMCs as compared to that in WT BMMCs. Given the role of PI3-K signals in mediating cytoskeletal organization in mast cells, we next tested whether the reduction in PI3-K signals was associated with a reduction in degranulation and migration. Following stimulation with kit-ligand and cross-linking of the IgE receptor, KSR−/− mast cells were found to have a 30–50% decrease in b-hexosaminidase release. Moreover, KSR−/− mast cells have up to a 5 fold reduction in migration to kit-ligand as measured over a range of kit-ligand concentrations. Collectively, the in vivo and in vitro studies suggest that KSR is an important regulatory kinase that may be a viable molecular target for modulating inflammatory mast cell functions.

Comparative analysis of the role of mast cells in murine asthma models using Kit‐sufficient mast cell‐deficient animals

Allergy ◽  
2021 ◽  
Author(s):  
Lea Pohlmeier ◽  
Sanchaita Sriwal Sonar ◽  
Hans‐Reimer Rodewald ◽  
Manfred Kopf ◽  
Luigi Tortola
Keyword(s):  
Mast Cell ◽  
Comparative Analysis ◽  
Mast Cells

The Role of Proopiomelanocortin-Derived Peptides in Skin Fibroblast and Mast Cell Functions

2006 ◽  
Vol 885 (1) ◽  
pp. 268-276 ◽  
Author(s):  
PATRIZIA TEOFOLI ◽  
ALESSANDRA FREZZOLINI ◽  
PIETRO PUDDU ◽  
ORNELLA PITÀ ◽  
ALAIN MAUVIEL ◽  
...  
Keyword(s):  
Mast Cell ◽  
Skin Fibroblast ◽  
Cell Functions

Mast cell heterogeneity

1984 ◽  
Vol 62 (6) ◽  
pp. 734-737 ◽  
Author(s):  
F. Shanahan ◽  
J. A. Denburg ◽  
J. Bienenstock ◽  
A. D. Befus
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Regulatory Peptides ◽  
Cell Heterogeneity ◽  
Cell Secretion ◽  
Biochemical Basis ◽  
Mucosal Mast Cells ◽  
Mast Cell Heterogeneity

Increasing evidence for the existence of inter- and intra-species mast cell heterogeneity has expanded the potential biological role of this cell. Early studies suggesting that mast cells at mucosal sites differ morphologically and histochemically from connective tissue mast cells have been confirmed using isolated intestinal mucosal mast cells in the rat and more recently in man. These studies also established that mucosal mast cells are functionally distinct from connective tissue mast cells. Thus, mucosal and connective tissue mast cells differ in their responsiveness to a variety of mast cell secretagogues and antiallergic agents. Speculation about the therapeutic use of antiallergic drugs in disorders involving intestinal mast cells cannot, therefore, be based on extrapolation from studies of their effects on mast cells from other sites. Regulatory mechanisms for mast cell secretion may also be heterogeneous since mucosal mast cells differ from connective tissue mast cells in their response to a variety of physiologically occurring regulatory peptides. The development of techniques to purify isolated mast cell sub-populations will facilitate future analysis of the biochemical basis of the functional heterogeneity of mast cells.

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