Mast Cells and Tumor Microenvironment

Abstract Increasing evidence indicates that a unique immune cell, the mast cell, accumulates in the stroma surrounding certain tumors, especially mammary and pancreatic adenocarcinoma, as well as melanoma. Many molecules secreted by mast cells could benefit the tumor in at least four ways: (1) angiogenin, heparin and vascular endothelial growth factor (VEGF), which induce neovascularization; (2) proteases that disrupt the surrounding matrix and facilitate metastases; (3) growth factors such as, epidermal growth factor (EGF), nerve growth factor (NGF), platelet derived growth factor (PDGF) and stem cell factor (SCF); (4) histamine, IL-10 and transforming growth factor-b (TGF-b), which are immunosuppressant, along with activation of certain dendritic cells that induce immunologic anergy. These actions could only occur through the unique ability of mast cells to release certain mediators selectively without degranulation. Blocking such release of pro-tumor mediators may constitute a novel therapeutic approach.