Crosstalk between Mast Cells and Pancreatic Cancer Cells Contributes to Pancreatic Tumor Progression

Abstract

Purpose To assess the clinical and pathological significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design Immunohistochemistry for tryptase was performed on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from cancer patients was compared to patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer conditioned media on mast cell migration was assessed. The effect of conditioned media from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell conditioned media on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results Mast cell infiltration was significantly increased in pancreatic cancer compared to normal pancreatic tissue [11.4±6.7vs.2.0±1.4(p<0.001)]. Increased infiltrating mast cells correlated with higher grade tumors (p<0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (p<0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell conditioned media induced pancreatic cancer cell migration, proliferation and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was in large part MMP-dependent. Conclusions Tumor infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promote tumor growth and invasion.

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

“…28,29 Our study further provides experimental evidence that primary human MC promote colon cancer growth by stimulating production of pro-tumorigenic mediators in a bidirectional manner. Thus far, most studies in human MC-cancer interaction were using MC cell lines (LAD2 and HMC-1) 30–35 with specific limitations that these cell lines are leukemia-derived (e.g. obtain a nature of cancer cells) and hardly express MC proteases or MC-specific receptors.…”

Mast Cells: Potential Positive and Negative Roles in Tumor Biology

“…The deleterious roles of mast cells were identified in studies of neoplasms affecting the skin, including malignant melanoma (30,59,60), Merkel cell carcinoma (61), and primary cutaneous lymphoma (58). Increased numbers of mast cells were also found in pancreatic adenocarcinomas (62)(63)(64); squamous cell carcinomas (SCC) of the esophagus (65), mouth (66), and lip (67) (29, 30, 58-60, 62, 64-66, 71, 75), the extent of angiogenesis, as assessed by staining of microvessels (in most cases by immunohistochemistry using anti-human CD31 or CD34 antibodies), was positively correlated with the numbers of mast cells per unit area of tissue. In some of these studies, mast cells were shown to express VEGF (29,30).…”

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

“…They support angiogenesis by expression of proangiogenic factors and by inhibition of ECM remodeling the MCs support tumor spread and metastasis. Tumor-associated mast cells are also regarded as potential therapeutic targets [124][125][126][127][128] and prognostic factor [129][130][131].…”