Cells from an aggressively growing primary tumor, the instigator, secrete the circulating signal osteopontin. This mobilizes a population of Sca-1⁺cKit^– BM progenitor cells that express high levels of the secreted glycoprotein GRN. The GRN⁺Sca-1⁺cKit^– BMCs travel to the site of inoculation of a second cancer cell type, the responder, that grows poorly in mice. GRN⁺Sca-1⁺cKit^– cells enhance the assembly of the tumor stoma by stimulating the differentiation of fibroblasts into αSMA-expressing myofibroblasts. The stroma, in turn, supports the successful growth of the otherwise quiescent or indolent responder cells, resulting in a proliferating stroma-rich carcinoma outgrowth (7). The process whereby an aggressive primary tumor promotes the outgrowth of another otherwise indolent tumor is called systemic instigation. Interrupting the paracrine GRN signal during systemic instigation or preventing the mobilization of the GRN⁺Sca-1⁺cKit^– BMCs might prove therapeutically useful in preventing the formation of reactive tumor stroma, thereby inhibiting tumor progression (7). The role of GRN⁺Sca-1⁺cKit^– BMCs as local regulators of tumor progression is compared to other proposed mechanisms of BM/tumor interaction. For example, the BM may provide progenitor cells directly; in the example shown, tumor fibroblasts secrete stromal-derived factor-1 (SDF), which mobilizes endothelial progenitor cells (EPC). These contribute to angiogenesis (16). Other hematopoietic progenitors, for example VEGFR1⁺ cells, may assist in the creation of prometastatic niches (17).