Placenta growth factor (PLGF) was initially cloned from a term placenta cDNA library. ?It is a member of the PDGF/VEGF family of growth factors that share a conserved pattern of eight cysteines. As a result of alternative splicing, four isoforms for PLGF has been described, PLGF-1 (PLGF-131), PLGF-2 (PLGF-152), PLGF-3 (PLGF-203), and PLGF-4 (PLGF-224).? While PLGF isoforms are present in most placental tissues, PLGF-2 is specific to early placenta and only PLGF-1 is found in the colon and mammary carcinomas.? The PLGFs are secreted, but PLGF-2 appears to remain cell attached unless released by heparin.? PLGF-2 binds to heparin with high affinity, whereas PLGF-1, PLGF-3, and PLGF-4 do not bind heparin. ?PLGF-2 is the only isoform found in mouse. PLGF binds to VEGF-R1 and neuropilins, but not to VEGF-R2. ?PLGF induces monocyte activation, migration, and production of inflammatory cytokines. ?PLGF plays a key role in the maternal vascular function during pregnancy. Circulating PLGF increases during pregnancy, reaching a peak in mid-`gestation. Low levels of PLGF have been associated with patients experiencing preeclampsia. ?High expression of PLGF has been associated to colorectal cancer (CRC), and its expression in CRC tissues correlates with high levels of MMP-9 and VEGF-R1. PLGF has been shown to increase tumor cell migration in lung cancer, leukemia, and melanoma cells. ?In colorectal cancer, PLGF induces tumor cell migration and invasion through upregulation of MMP9.? PLGF is expressed in the majority of medulloblastomas, and high expression of PLGF receptor neuropilin 1 (Nrp1) correlates with poor survival in patients. In a mouse model, PLGF/Nrp1 blockade provided direct antitumor effects in vivo, including medulloblastoma regression, decreased metastasis, and increased survival.