Mast cells: The JEKYLL and HYDE of tumor growth

Mast cells accumulate in the stroma surrounding certain tumors, especially mammary adenocarcinoma, and molecules they secrete could benefit the tumor. These include heparin, interleukin-8 (IL-8) and vascular endothelial cell growth factor (VEGF), which induce neovascularization, histamine, which is an immunosuppressant, mitogenic factors, such as platelet-derived growth factor (PDGF), nerve GF (NGF), stem-cell factor (SCF), and proteases, which disrupt the surrounding matrix and facilitate metastases. By contrast, mast-cell mediators detrimental to the tumor include cytokines, such as IL-1, IL-4, IL-6 and tumor necrosis factor-α (TNF-α), which can induce apoptosis of tumor cells, tryptase, which stimulates protease-activated receptors and induces inflammation, and chondroitin sulfate, which could act as a decoy and inhibit metastases. We propose that beneficial and destructive mediators are either released from separate granules or much smaller vesicles regulated by selectively distinct signals, such as tumor-derived oxidized polyamines or nitric oxide from new endothelial cells. This dual role of mast cells could be additive to that of tumor infiltrating macrophages, the 'polarization' of which to M2 type appears to be conducive to tumor growth.