Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings

Abstract

Paul Ehrlich, a German scientist, discovered what is known as the mast cell in the late 1800's, which has proven to be an important player in the immune system of vertebrates. Mast cells are ubiquitous throughout the tissues of the human body and play numerous roles, both beneficial and destructive. We know they are important in our army of immunity warrior cells, which defend us against viruses, bacteria and parasitic invaders. They are also very well known for the havoc they wreak, causing uncomfortable symptoms due to their release of histamine and other mediators which cause the all too familiar itching, sneezing, urticaria and rhinorrhea of allergic responses. Mast cell activities are diverse and include painful inflammatory reactions in autoimmune conditions such as rheumatoid arthritis. In the gastrointestinal system, mast cells are implicated in diverse actions such as increased gastric acid secretion, polyp formation and uncomfortable conditions such as Irritable Bowel Syndrome. The role of immunology and mast cells in these areas is intriguing but less well understood than their role in allergic responses. Because mast cells have been implicated in both physiologic as well as pathogenic processes, they have been the subjects of avid study. Review of the current literature on mast cell biology reveals that there are many studies of their presence within the tumor microenvironment and evidence, which supports mast cell influence on tumor angiogenesis, tumor invasion, and immune suppression. The studies reviewed in this article concentrate largely on mast cells in human GI malignancies. This review also provides background information regarding mast cells, such as their origination, their location within the body, how they are activated and how they function as mediators.

Figure 1

Newly identified protective (green) or detrimental (red) roles of mast cells and mast cell products in biological responses in mice. AAA, abdominal aortic aneurysm; CPA3, carboxypeptidase A3; ET-1, endothelin-1; IgE, immunoglobulin E; IL, interleukin; MC, mast cell; MCP, mast cell protease; NLN, neurolysin; NT, neurotensin; SMC, smooth muscle cell; TNF, tumor necrosis factor; Tpsb2, tryptase β2. [Reprinted with permission from Nature Immunology, New developments in mast cell biology 2008; 9: 1215-23.]

Figure 2

Immunohistochemistry for chymase and tryptase in human tumor biopsies. Both proteases display increased immunoreactivity in cholangiocarcinoma samples compared to nonmalignant samples. *P<0.05 vs. nonmalignant. Data are mean ± SEM of 3 experiments. Org. magnification ×40. Unpublished observations from Alpini & Francis et al. 2010

Figure 3

Mast cells infiltrate human pancreatic adenocarcinoma. Immunohistochemistry (magnification, ×400) for mast cell-specific tryptase (seen with dark red staining) in normal pancreas from a patient with a benign cystic neoplasm (A), an adjacent histologically normal area of pancreas from a patient with pancreatic adenocarcinoma (B), and pancreatic adenocarcinoma (C). (D) tryptase-positive mast cells were counted at 400× magnification in 12 pancreatic cancer specimens and compared with the adjacent normal pancreas and 10 normal areas of pancreas from patients with benign disease. Mast cell infiltration was greater in cancer versus adjacent normal (P<0.01) and in cancer versus benign normal (P<0.001). Mast cell infiltration was greater in adjacent normal versus benign normal (P<0.05). (E) serum tryptase activity was measured by a quantitative spectrophotometric assay in 36 patients with pancreatic cancer and compared with 10 patients with benign pancreatic disease (*, P<0.05; **, P<0.001). [Reprinted with permission from Clinical Cancer Research, Crosstalk between mast cells and pancreatic cells contributes to pancreatic cancer progression 2010;16:2257-65.]