Targeting Mast Cells Tryptase in Tumor Microenvironment: A Potential Antiangiogenetic Strategy

Ammendola, Michele; Leporini, Christian; Marech, Ilaria; Gadaleta, Cosmo Damiano; Scognamillo, Giovanni; Sacco, Rosario; Sammarco, Giuseppe; Sarro, Giovambattista De; Russo, Emilio; Ranieri, Girolamo

doi:10.1155/2014/154702

Cited by 61 publications

(58 citation statements)

References 148 publications

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“…According to these data, targeting MCs is currently under investigation. Actually, therapies with tyrosine kinase inhibitors (imatinib and masitinib) for c-Kit receptor-targeted action and MC tryptase inhibitors (gabexate mesylate, nafamostat mesylate and tranilast) represent the most used clinical treatments against MCs in cancer [8,60,61,62,63,64,65]. …”

Section: Targeting Mast Cells In Cancer Therapymentioning

confidence: 99%

Mast Cell-Targeted Strategies in Cancer Therapy

Ammendola

Sacco

Sammarco

et al. 2016

Transfus Med Hemother

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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.

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Section: Targeting Mast Cells In Cancer Therapymentioning

confidence: 99%

Mast Cell-Targeted Strategies in Cancer Therapy

Ammendola

Sacco

Sammarco

et al. 2016

Transfus Med Hemother

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“…Specifically, tryptase, because of its properties in tissue degradation, may play a pivotal role in the angiogenesis and metastatization [2,3]. However, the literature lacks reports on ST levels in MM, in contrast to pancreatic cancer and breast cancer, where ST levels correlate with tumor progression [2].…”

Section: Received 1 December 2015 Accepted 23 December 2015mentioning

confidence: 99%

“…Patients up to 60 years showed median ST levels of 4.2 ng/ml, whereas patients of at least 61 years showed median ST of 4.3 ng/ml. On performing multiple logistic regression, only the variables Breslow (P = 0.04) and ulceration (P = 0.001) reached statistical significance.The release of chemokines, stem cell factors, and histamine by mast cells supports the proliferation of melanocytes and ST levels are commonly considered to be related to the total number of mast cells [2]. Specifically, tryptase, because of its properties in tissue degradation, may play a pivotal role in the angiogenesis and metastatization [2,3].…”

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Serum tryptase levels in melanoma patients

et al. 2016

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We have read with much interest the article of Siiskonen et al. [1]. For this reason, we would like submit our observation on the role of serum tryptase (ST) levels in patients with melanoma (MM).We included patients in whom an MM or an MM metastasis had been removed recently to evaluate ST levels. ST was assessed within 20 days after the removal of the primary MM or MM metastasis. All samples of ST were assayed at the same laboratory and ST less than 11.4 ng/ml was considered to be within the normal range. We excluded from the analysis patients with anaphylaxis, hereditary/acquired angioedema, immunological dysfunctions, clonal/nonclonal hematologic disorders and internal malignancies, as well as patients with atopy and/ or asthma. We also excluded patients with recent intake of antihistamines (≤ 30 days).Sex, age (≤ 60 or ≥ 61), anatomical sites (axial versus peripheral sites), Breslow thickness (≤ 1 or ≥ 1.01 mm), ulceration, and mitotic rate were used as variables for each patient. However, we considered only the variables sex and age for metastatic patients.A total of 38 patients (25 males and 13 females) were included. The median age was 60 years (range between 20 and 85 years); the anatomical site was axial in 25 patients and peripheral in 11 patients. In one patient, a dermal metastasis had been removed from the leg and in another, a liver metastasis had been removed.Median Breslow thickness was 0.4 mm (range between 0 and 8), ulceration was present in six patients, and mitotic rate was at least 1/mm 2 in nine patients. The median ST level was 4.8 ng/ml (range between 0.98 and 13.4). In 36 patients, ST was less than 11.4 ng/ml, whereas only two patients showed high levels of ST: one patient with xeroderma pigmentosum (XP) and another one with a nodular MM, who presented the highest Breslow thickness of the cohort. In terms of Breslow thickness, the median ST was 4.3 ng/ml in MM, with a Breslow up to 1.00 mm, 4 ng/ml in MM, at least 1.01 mm and 3.4 ng/ml in metastatic patients. Considering the ulceration, the median ST was 4.6 ng/ml in MM without ulceration and 3.0 ng/ml in ulcerated MM. For the mitotic rate, the median ST levels were 4.3 ng/ml in MM with mitotic rate less than 1/mm 2 and 4.1 ng/ml in MM with mitotic rate of at least 1/mm 2 . The median level of ST was 4.3 ng/ml in MM of the axial sites and 5.3 ng/ml in MM of the peripheral sites. Patients up to 60 years showed median ST levels of 4.2 ng/ml, whereas patients of at least 61 years showed median ST of 4.3 ng/ml. On performing multiple logistic regression, only the variables Breslow (P = 0.04) and ulceration (P = 0.001) reached statistical significance.The release of chemokines, stem cell factors, and histamine by mast cells supports the proliferation of melanocytes and ST levels are commonly considered to be related to the total number of mast cells [2]. Specifically, tryptase, because of its properties in tissue degradation, may play a pivotal role in the angiogenesis and metastatization [2,3]. However, the literature lacks reports on ST lev...

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“…Tryptase and chymase are the most common mast cell granules components studied in angiogenesis. Gabexate mesylate, nafamostat mesylate, and tranilast are mast cells inhibitors recently studied as new promising antiangiogenic agents (Ammendola et al 2014). Disodium cromolyn, another mast cell stabilizer, has a widely accepted antitumor effects in several tumor types as cholangiocarcinoma (Johnson et al 2016), pancreatic cancer (Kim et al 2012) or breast malignancies (Samoszuk and Corwin 2003).…”

Section: Introductionmentioning

confidence: 99%

The Hidden Side of Disodium Cromolyn: from Mast Cell Stabilizer to an Angiogenic Factor and Antitumor Agent

Cimpean

Raica

2016

Arch. Immunol. Ther. Exp.

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Scattered data suggested that disodium cromolyn, well known as a mast cell stabilizer shows some effects on tumor cells and tumor-associated newly formed vascular networks. Most of these studies used tumor cell lines assessed by in vitro studies. Nor disodium cromolyn effects on melanoma cell lines were studied yet, neither its influence on recruited tumor blood vessels or angiogenic growth factors expression. We designed here a study regarding disodium cromolyn effects on A375 melanoma tumor cells implanted on chick embryo chorioallantoic membrane (CAM) and on blood vessels recruited by the experimental melanoma in the absence of mast cells, knowing that within CAM, the existence of mast cells are not certified yet. We also assessed the role of disodium cromolyn on the expression of several angiogenic growth factors. Disodium cromoglycate differentially acts on tumor cells and blood vessels. Extensive necrotic areas of experimental melanoma together with an increased number of peritumor blood vessels were observed in treated specimens as compared with untreated tumors. Disodium cromolyn inhibited VEGF and PDGF-BB expression, and had no effects on EG VEGF expression between treated and non treated specimens in a mast cells free microenvironment. Our results sustain the direct antitumor effects of sodium cromolyn and suggest the involvement of several growth factors in the recruitment of tumor vessels by A375 melanoma tumor cells. The expression of growth factors is differentially influenced by sodium cromolyn treatment.

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Targeting Mast Cells Tryptase in Tumor Microenvironment: A Potential Antiangiogenetic Strategy

Cited by 61 publications

References 148 publications

Mast Cell-Targeted Strategies in Cancer Therapy

Mast Cell-Targeted Strategies in Cancer Therapy

Serum tryptase levels in melanoma patients

The Hidden Side of Disodium Cromolyn: from Mast Cell Stabilizer to an Angiogenic Factor and Antitumor Agent

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