Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer

Figure 1

Overview of mast cell development, heterogeneity, and activation. Mast cells arise in the bone marrow from hematopoietic stem cells (HSC) via a multipotent progenitor (MPP), which can become a mast cell-committed progenitor (MCP) that exits the bone marrow and migrates to peripheral tissues to complete maturation. Several pathways have been described for murine and human mast cell origin. In mice, MCPs may be derived directly from MPPs or from common myeloid progenitors (CMP). Mast cells may also be derived from the granulocyte/monocyte progenitor (GMP) via an intermediate progenitor (BMCP), identified only in the spleen of C57BL6 mice, which gives rise to basophils and mast cells. In humans, it has been postulated that mast cells originate from a yet unidentified uncommitted progenitor that gives rise to a mast cell/monocyte-committed progenitor (MC/MP) in bone marrow. Alternatively, an MCP population that gives rise exclusively to mast cells has recently been identified in blood. Final differentiation occurs in peripheral tissues, where microenvironmental factors determine the phenotype of the mature mast cells. Mast cells exhibit marked phenotypic and functional heterogeneity. Two major subtypes have been described in both rodents and humans, in the former as mucosal and connective tissue mast cells and in the latter as tryptase- and chymase-rich mast cells (MC_TC) and those that mainly contain tryptase (MC_T). The right end diagram illustrates the distinct classes of bioactive molecules and their temporality of release upon mast cell activation in tissues. See text for a more detailed explanation.