The colony-stimulating factors and cancer

Abstract

The colony-stimulating factors (CSFs) are the master regulators of granulocyte and macrophage populations. There are four different aspects of the connection between the CSFs and cancer: (a) the CSFs can accelerate the regeneration of protective white cells damaged by chemotherapy; (b) the CSFs can mobilize stem cells to the peripheral blood in convenient numbers for transplantation; (c) the CSFs can enhance anticancer immune responses and (d) the CSFs are potentially involved in the genesis of the myeloid leukemias.

Figure 1

The family tree of granulocytes and macrophages. Hematopoietic stem cells are self-generating cells and also produce 100-fold higher numbers of blast colony-forming cells each of which can generate up to a thousand committed progenitor cells in various lineages (only the granulocyte-macrophage and dendritic lineages are shown). In turn, each progenitor cell can generate up to 10⁴ maturing progeny. The ability of one stem cell to produce 109 progeny is rarely required. Shown in boxes are the cytokines controlling each differentiation/proliferation step. G = granulocytic lineage; GM = granulocyte-macrophage lineage; M = macrophage lineage; DC = dendritic cell lineage. SCF = stem cell factor, TPO = thrombopoietin, FL = Flt3 ligand, IL-6 = interleukin-6, G-CSF = granulocyte colony-stimulating factor, GM-CSF = granulocyte-macrophage colony-stimulating factor, IL-3 = interleukin-3, M-CSF = macrophage colony-stimulating factor.

Figure 2

The five major actions of CSFs on responding granulocyte-macrophage populations. Several different regions of the cognate CSF membrane receptors are needed to initiate the various responses: (a) The CSFs prevent death in the population by suppressing apoptosis, (b) The CSFs are required to stimulate every cell division in a dose-responsive manner, (c) The CSFs have some ability to influence lineage commitment decisions, (d) The CSFs can initiate and regulate maturation of cells in these lineages, and (e) The CSFs can strongly stimulate the functional activity of mature granulocytes and macrophages. IL-1 = interleukin-1, IFNγ = interferonγ, TNFα = tumor necrosis factor α, PA = plasminogen activator. This figure was adapted from reference 27, Metcalf, D. The colony-stimulating factors and cancer. Nat Rev Cancer 2010; 10:425-34.