Cytokines can stimulate neovascularization by recruiting stromal cells to newly formed blood vessels. Tumor cells can co-opt this process through deregulated cytokine signaling to stromal cells, the recruitment of which supports the tumor vasculature and promotes an angiogenic phenotype. Xue and colleagues analyzed the role of one such cytokine, platelet-derived growth factor-BB (PDGF-BB, a dimer of PDGF-B), to promote angiogenesis, growth, and stromal expansion by overexpressing PDGF-BB in xenografted cancer cells. PDGF-BB–expressing tumors grew at a significantly faster rate and exhibited a significantly higher degree of stromal infiltration and microvessel density. Surprisingly, increased blood cell precursor proliferation was specifically observed in the spleens and livers of mice with PDGF-BB–expressing tumors, which also exhibited increased concentrations of erythropoietin (EPO), a hormone normally produced primarily in the kidney that stimulates erythropoiesis. The authors used an EPO reporter gene construct and specific PDGF receptor (PDGFR) inhibitors to demonstrate that PDGF-BB activates EPO transcription...

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