Tumor development requires accomplices among white blood cells. Other than macrophages, mast cells have been observed to support the outgrowth of certain
neoplasias because of their proangiogenic properties. In some
tumor settings, however, mast cells may have a protective role, exerted by their proinflammatory mediators. In
prostate cancer, no conclusive data on mast cell function were available. Here, we discuss recent work on the role of mast cells in mouse and human
prostate cancer, showing that mast cells can behave alternatively as dangerous promoters, innocent bystanders, or essential guardians of
tumors, according to the stage and origin of transformed cells. In particular, mast cells are essential for the outgrowth of early-stage
tumors due to their
matrix metalloproteinase-9 production, become dispensable in advanced-stage, post-epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate
tumor variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the
ligand Stem cell factor and offers the chance of curing early-stage disease while preventing
neuroendocrine tumors using c-Kit-targeted
therapy. This review discusses the implications of these findings on the advocated mast cell-targeted
cancer therapy and considers future directions in the study of mast cells and their interactions with other c-Kit-expressing cells.