Mast Cell Tryptase Contributes to Pancreatic Cancer Growth through Promoting Angiogenesis via Activation of Angiopoietin-1.

Xiangjie Guo,Liqin Zhai,Qiang Zeng,Jieru Shi,Ruobing Xue,Cairong Gao

doi:10.3390/ijms17060834

Xiangjie Guo, Liqin Zhai + Show 4 more

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https://doi.org/10.3390/ijms17060834

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Abstract

Pancreatic cancer is a highly lethal malignancy and one of the leading causes of cancer-related death. During the development and progression of cancer, tumor angiogenesis plays a crucial role. A great deal of evidence has revealed that human mast cells (MCs) contributed to tumor angiogenesis through releasing several pro-angiogenetic factors, among which tryptase is one of the most active. However, the role of mast cell tryptase (MCT) in human pancreatic cancer angiogenesis is still not well documented. In this study, we examined the MCT levels in serum from pancreatic cancer patients and evaluated the correlationship of the MCT level and tumor angiogenesis. In addition, the effect of MCT on endothelial cell proliferation and tube formation was investigated both in vitro and in nude mice bearing pancreatic tumor. It was found that MCT contributes to endothelial cell growth and tube formation via up-regulation of angiopoietin-1 expression. Moreover, using the MCT inhibitor nafamostat, tryptase-induced angiogenesis was obviously suppressed both in vitro and in vivo. Our findings suggest that MCT plays an important role in pancreatic cancer angiogenesis and tumor growth via activating the angiopoietin-1 pathway, and tryptase inhibitors may be evaluated as an effective anti-angiogenetic approach in pancreatic cancer therapy.

Highlights

Pancreatic cancer is one of the most common malignancies worldwide, in which pancreatic ductal adenocarcinoma (PDAC) is the most common type [1]
To investigate whether mast cell tryptase (MCT) was involved in pancreatic cancer development, we firstly examined the expression level of MCT in serum from pancreatic cancer patients and healthy people
It was found that the increased MCT levels were correlated with higher microvascular density in pancreatic cancer patients (Figure 1D)

Summary

Introduction

Pancreatic cancer is one of the most common malignancies worldwide, in which pancreatic ductal adenocarcinoma (PDAC) is the most common type [1]. As there is still a less effective therapy method, it is urgent for us to improve our understanding of pancreatic cancer development and progression. A better understanding of the mechanism of pancreatic cancer pathogenesis will facilitate early detection and development of effective treatments for this deadly disease. Kankkunen et al found that there were significantly more tryptase-containing MCs in malignant breast carcinomas compared to benign lesions, suggesting that MC density is correlated with the extent of tumor growth by promoting angiogenesis [9,10]. The correlations between MCT and angiogenesis in pancreatic cancer and the underlying mechanism are still not clear. Exploring whether the MCT is responsible for tumor angiogenesis could provide new diagnostic markers and therapeutic targets for cancers

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