Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

Abstract

Abstract:Background. Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique. Methods. Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII. Results. The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis. Conclusions. All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

“…8 -11 Mast cells produce a broad repertoire of cytokines to regulate inflammatory responses, growth factors to stimulate blood vessels and fibroblasts, and enzymes capable of releasing growth factors from extracellular matrix. 5,8 -11,27,28,42 In other human tumors studies it has been shown that mast cell function is complicated with both pro -and antitumor effects, 35,[43][44][45][46] but to the best of our knowledge no studies have previously described differential roles of mast cells depending on the local microenvironment within the same clinical material. It is well established that inflammatory cell types within or surrounding tumors such as tumor-associated macrophages 47 and more lately also neutrophils 48 can be educated by growth factors and cytokines within the tumor microenvironment to acquire pro-or antitumor properties.…”

Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer

“…In contrast to the findings in experimentally induced malignancies, some studies have suggested promote that mast cells tumour progression. For instance, mast cell infiltration correlates well with tumour angiogenesis and metastases in gastric cancer (Yano et al, 1999), colorectal cancer (Lachter et al, 1995), pulmonary adenocarcinoma (Takanami et al, 2000) and renal cell carcinoma (Tuna et al, 2006). In PCas, mast cell infiltration correlates with poor prognosis, suggesting that mast cells may promote tumour progression.…”

Association between mast cells of different phenotypes and angiogenesis in colorectal cancer

“…It has been reported that MCs are involved and deregulated in number and phenotype in immune events and in several pathologies (20)(21)(22), including cancer (2,5,(8)(9)(10)12). Although it is widely accepted that these cells accumulate at the site of solid tumours and are able to modulate tumour behaviour, the functional role of each MC phenotype is controversial.…”

“…By scanning the intratumoral zone and the invasive edge, we observed that the number of MCs of both phenotypes was significantly higher in the invasive edge than in the intratumoral zone in all Astler-Coller stages, with MCt being the prominent phenotype. The increased number of MCs in the invasive edge may be due to MC uninterrupted renewal from stem cells leaving blood vessels and beginning their differentiation into MCs in the connective tissue while migrating towards the tumour, most probably attracted by chemokines released into the tumoral microenvironment (8). In addition, MCs are located in connective tissue surrounding tumoral nests; the smaller the amount of connective tissue present in the intratumoral zone with respect to that in the invasive edge, the lower the number of MCs recorded in a determined area will be.…”

“…The first proposes that MCs may contribute to neoplastic progression by secreting proteases and cytokines, which increase tumour growth, angiogenesis and metastasis (7)(8)(9). The second suggests that MCs may impair tumour development, inducing tumour cell cytotoxicity (10) or inhibiting tumour growth and metastasis (11)(12)(13)(14)(15).…”