Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Siiskonen, Hanna; Poukka, Mari; Bykachev, Andrey; Tyynelä-Korhonen, Kristiina; Sironen, Reijo; Pasonen‐Seppänen, Sanna; Harvima, Ilkka T.

doi:10.1097/cmr.0000000000000192

Cited by 65 publications

(75 citation statements)

References 47 publications

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“…In this respect, these findings confirm the results of Siiskonen et al [1] highlighting that this serine protease may also be serologically the expression of a protective role. However, our results also seem to highlight that ST may play a role in the early stage of the tumorigenesis.…”

supporting

confidence: 94%

“…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).…”

mentioning

confidence: 90%

“…

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.

…”

mentioning

confidence: 95%

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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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confidence: 94%

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Serum tryptase levels in melanoma patients

et al. 2016

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“…Examples of the latter include breast cancer [17, 18], non-small-cell lung carcinoma [19], diffuse large B-cell lymphoma [20] and ovarian cancer [21]. In melanoma, partly conflicting clinical findings have been published (reviewed in [10]), with some studies indicating a detrimental impact of mast cells [22-24] whereas others have reported a positive correlation between mast cell presence and good prognosis [25]. …”

Section: Introductionmentioning

confidence: 99%

Mast cells promote melanoma colonization of lungs

et al. 2016

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Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre+ R-DTA+ mice, in which the deficiency of mast cells is independent of c-kit defects. Melanoma cells (B16.F10) were administered either subcutaneously or intravenously into Mcpt5-Cre+ R-DTA+ mice or Mcpt5-Cre− R-DTA+ littermate controls, followed by the assessment of formed tumors. In the subcutaneous model, mast cells were abundant in the tumor stroma of control mice but were absent in Mcpt5-Cre+ R-DTA+ mice. However, the absence of mast cells did not affect tumor size. In contrast, after intravenous administration of B16.F10 cells, melanoma colonization of the lungs was markedly reduced in Mcpt5-Cre+ R-DTA+ vs. Mcpt5-Cre− R-DTA+ animals. Decreased melanoma colonization of the lungs in Mcpt5-Cre+ R-DTA+ animals was accompanied by increased inflammatory cell recruitment into the bronchoalveolar lavage fluid, suggesting that mast cells suppress inflammation in this setting. Further, qPCR analysis revealed significant alterations in the expression of Twist and E-cadherin in lungs of Mcpt5-Cre+ R-DTA+ vs. control Mcpt5-Cre− R-DTA+ animals, suggesting an impact of mast cells on epithelial-mesenchymal transition. In conclusion, this study reveals that mast cells promote melanoma colonization of the lung.

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“…A low density of mast cells in invasive melanomas correlates with a poor prognosis, but the mast cell count is not correlated with survival in superficial melanomas [197]. In prostate cancer, mast cells are initially protumorigenic, but become dispensable at later stages [198, 199].…”

Section: Mast Cells In the Immune Landscape Of Cancermentioning

confidence: 99%

Physiological Roles of Mast Cells: Collegium Internationale Allergologicum Update 2019

Varricchi

Rossi

Galdiero

et al. 2019

Int Arch Allergy Immunol

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Mast cells are immune cells which have a widespread distribution in nearly all tissues. These cells and their mediators are canonically viewed as primary effector cells in allergic disorders. However, in the last years, mast cells have gained recognition for their involvement in several physiological and pathological conditions. They are highly heterogeneous immune cells displaying a constellation of surface receptors and producing a wide spectrum of inflammatory and immunomodulatory mediators. These features enable the cells to act as sentinels in harmful situations as well as respond to metabolic and immune changes in their microenvironment. Moreover, they communicate with many immune and nonimmune cells implicated in several immunological responses. Although mast cells contribute to host responses in experimental infections, there is no satisfactory model to study how they contribute to infection outcome in humans. Mast cells modulate physiological and pathological angiogenesis and lymphangiogenesis, but their role in tumor initiation and development is still controversial. Cardiac mast cells store and release several mediators that can exert multiple effects in the homeostatic control of different cardiometabolic functions. Although mast cells and their mediators have been simplistically associated with detrimental roles in allergic disorders, there is increasing evidence that they can also have homeostatic or protective roles in several pathophysiological processes. These findings may reflect the functional heterogeneity of different subsets of mast cells.

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Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Cited by 65 publications

References 47 publications

Serum tryptase levels in melanoma patients

Serum tryptase levels in melanoma patients

Mast cells promote melanoma colonization of lungs

Physiological Roles of Mast Cells: Collegium Internationale Allergologicum Update 2019

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