Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway

Background: placenta growth factor (plgf),a dimeric glycoprotein with 53% homology to vegf,binds to vegf receptor-1 (flt-1),but not to vegf receptor-2 (flk-1),and may function by modulating vegf activity. we previously have showed that plgf displays prognostic value in colorectal cancer (crc) but the mechanism remains elucidated. results: overexpression of plgf increased the invasive/migration ability and decreased apoptosis in crc cells showing flt-1 expression. increased migration was associated with increasing mmp9 via p38 mapk activation. tumors grew faster,larger; with higher vascularity from plgf over-expression cells in xenograft assay. in two independent human crc tissue cohorts,plgf,mmp9,and flt-1 expressions were higher in the advanced than the localized disease group. plgf expression correlated with mmp9,and flt-1 expression. crc patients with high plgf and high flt-1 expression in tissue had poor prognosis. conclusion: plgf/flt-1 signaling plays an important role in crc progression,blocking plgf/flt-1 signaling maybe an alternative therapy for crc. © 2013 wei et al.; licensee biomed central ltd.