Mast Cell Positivity to Tryptase Correlates with Metastatic Lymph Nodes in Gastrointestinal Cancer Patients Treated Surgically

Ammendola, Michele; Sacco, Rosario; Donato, Giuseppe; Zuccalà, Valeria; Russo, Emilio; Luposella, Maria; Vescio, G; Rizzuto, Antonia; Patruno, Rosa; Sarro, Giovambattista De; Montemurro, Severino; Sammarco, Giuseppe; Ranieri, Girolamo

doi:10.1159/000351145

Cited by 58 publications

(55 citation statements)

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“…Previous studies have demonstrated that angiogenesis and Ki-67-positive fraction are essential for the development and progression of tumours (27)(28)(29)(30)(31). In addition, numerous studies have suggested that increased tissue MVD and Ki-67 proliferation index, which were individually assessed, were correlated with a poor prognosis in PDACP (21,22).…”

Section: Discussionmentioning

confidence: 99%

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

et al. 2015

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Abstract. Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T) [2][3] Node (N) 0-1 Metastasis (M) 0 were recruited into the present study and subsequently underwent surgery. PDAC tissue and adjacent normal tissue (ANT), resected during surgery, were evaluated using immunohistochemistry and image analysis methods to determine MVD, endothelial area (EA) and Ki-67 expression, which is an indicator of cell proliferation rate. The results demonstrated a correlation between the above parameters with each other as well as the main clinico-pathological features of PDAC. Significant differences were identified in MVD, EA and Ki-67 proliferation index between PDAC and ANT. It was demonstrated that MVD, EA and Ki-67 proliferation index were significantly correlated with each other in tumour tissue (r=0.69-0.81; P=0.001-0.003). However, no other significant correlations were identified. These data therefore suggested that angiogenesis and cell proliferation rate were significantly increased in PDAC compared with ANT, which provides a biological basis for the potential use of novel combinations of angiogenesis inhibitors and anti-proliferative chemotherapeutic drugs in the treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

et al. 2015

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“…Accordingly, as most tumors contain inflammatory cell infiltrates, often including abundant MCs, the question about the possible contribution of MCs to tumor development has progressively been emerging [31, 39]. MCs have been recognized as one of the earliest cell types to infiltrate many developing tumors, particularly malignant melanoma and breast and colorectal cancer (CRC) [8, 17, 21, 23, 40, 70, 71]. Ample evidence highlights that MCs accumulate predominantly around several types of tumors, at the boundary between malignant and healthy tissues [8, 17].…”

Section: Role Of Mast Cell Tryptase In Angiogenesis and Tumor Growthmentioning

confidence: 99%

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

Ammendola

Leporini

Marech

et al. 2014

BioMed Research International

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Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (mainly tryptase). In fact, in several animal and human malignancies, MCs density is highly correlated with tumor angiogenesis. In particular, tryptase, an agonist of the proteinase-activated receptor-2 (PAR-2), represents one of the most powerful angiogenic mediators released by human MCs after c-Kit receptor activation. This protease, acting on PAR-2 by its proteolytic activity, has angiogenic activity stimulating both human vascular endothelial and tumor cell proliferation in paracrine manner, helping tumor cell invasion and metastasis. Based on literature data it is shown that tryptase may represent a promising target in cancer treatment due to its proangiogenic activity. Here we focused on molecular mechanisms of three tryptase inhibitors (gabexate mesylate, nafamostat mesylate, and tranilast) in order to consider their prospective role in cancer therapy.

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“…In recent years, many findings have confirmed that mast cell accumulation correlates with increasing density of microvessels [51]. Mast cell activity facilitating tumorigenesis includes production of factors that support the process of forming a new vascular system within the site of tumor formation.…”

Section: Discussionmentioning

confidence: 93%

Association of infiltrating cells with microvessel density in oral squamous cell carcinoma

Stasikowska-Kanicka¹,

Wągrowska-Danilewicz²,

Danilewicz³

2017

pjp

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Several lines of evidence indicate that immune cells in the tumor microenvironment play an important role in regulating tumor progression. An immunohistochemical method was used to examine the abundance of natural killer (NK) cells, mucosal dendritic cells (DCs), macrophages, mast cells, and microvessel density in 78 cases of oral squamous cell carcinoma (OSCC): with better prognosis -OSCCBP (n = 37), and with poorer prognosis -OSCCPP (n = 41), and 18 controls. The mean numbers of macrophages and microvessels were significantly higher in the OSCCPP group in comparison to both OSCCBP and control groups. The mean number of NK cells, mast cells and DCs was lower in the OSCCPP group in comparison to the OSCCBP group, but there were no statistically significant differences between mean numbers of NK cells in tested groups. Statistically significant correlations between the number of DCs and NK cells and mast cells, as well as between microvessel density and numbers of macrophages, DCs and mast cells were revealed in both OSCCPP and OSCCBP groups. In conclusion, our findings revealed an association between the number of infiltrating cells and oral cancer prognosis. Moreover, our results suggest that the infiltrating cells (macrophages, Langerhans and mast cells) may be involved in the process of angiogenesis.

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Mast Cell Positivity to Tryptase Correlates with Metastatic Lymph Nodes in Gastrointestinal Cancer Patients Treated Surgically

Cited by 58 publications

References 58 publications

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

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

Association of infiltrating cells with microvessel density in oral squamous cell carcinoma

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