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Human vascular endothelial growth factor receptor 1 (VEGFR-1 or Flt-1) is widely expressed in normal and pathological tissues and is involved in the pathogenesis of tumors and inflammatory diseases. In human cancers, VEGFR-1-mediated signaling is responsible for direct tumor activation and angiogenesis. VEGFR-1-mediated activation of non-malignant supporting cells, particularly stromal cells, dendritic cells, hematopoietic cells, and macrophages, may also be important for cancer pathogenesis. It has also been hypothesized that VEGFR-1 promotes the development of cancer metastasis through activation and pre-metastatic localization in distant organs of VEGFR-1-expressing bone marrow-derived hematopoietic progenitor cells.