Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated with Angiogenesis in Surgically-Treated Gastric Cancer Patients.

Giuseppe Sammarco,Emre Albayrak,Rosario Sacco,Pietro Milella,Girolamo Ranieri,Rosa Patruno,Cosmo Damiano Gadaleta,Michele Ammendola,Valeria Zuccalà

doi:10.3390/ijms19041176

Abstract

Mast cells and macrophages can play a role in tumor angiogenesis by stimulating microvascular density (MVD). The density of mast cells positive to tryptase (MCDPT), tumor-associated macrophages (TAMs), and MVD were evaluated in a series of 86 gastric cancer (GC) tissue samples from patients who had undergone potential curative surgery. MCDPT, TAMs, and MVD were assessed in tumor tissue (TT) and in adjacent normal tissue (ANT) by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and, in particular for TT, with important clinico-pathological features. In TT, a significant correlation between MCDPT, TAMs, and MVD was found by Pearson t-test analysis (p ranged from 0.01 to 0.02). No correlation to the clinico-pathological features was found. A significant difference in terms of mean MCDPT, TAMs, and MVD between TT and ANT was found (p ranged from 0.001 to 0.002). Obtained data suggest MCDPT, TAMs, and MVD increased from ANT to TT. Interestingly, MCDPT and TAMs are linked in the tumor microenvironment and they play a role in GC angiogenesis in a synergistic manner. The assessment of the combination of MCDPT and TAMs could represent a surrogate marker of angiogenesis and could be evaluated as a target of novel anti-angiogenic therapies in GC patients.

Highlights

Mast cells (MCs) can play a role in tumor angiogenesis and their involvement has been found in spontaneous animal tumor models and human malignancies [1,2,3]
MCs were scattered in the stromal microenvironment and it was evident that MCs density positive to tryptase (MCDPT) were increased in tumor tissue (TT) vs. adjacent normal tissue (ANT) (Figure 1A vs. Figure 1B)
Substantial data has indicated the key role of angiogenesis in gastric cancer (GC) development and progression, but little data related to the role of both MCDPT and tumor-associated macrophages (TAMs) in GC angiogenesis have been published [40,51,52]

Summary

Introduction

Mast cells (MCs) can play a role in tumor angiogenesis and their involvement has been found in spontaneous animal tumor models and human malignancies [1,2,3]. It is well demonstrated that tryptase binds protease-activated receptor-2 (PAR-2) expressed on ECs, stimulating microvascular formation [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. Ms2 are identified as tumor-associated macrophages (TAMs) and they play a role as pro-angiogenic cells [39,40]. Ms induce angiogenesis by producing and releasing metalloproteinase-9 (MMP-9) that is able to degrade the extracellular matrix and cause the release of VEGF [43,44]

Methods

Results

Conclusion