Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway
Journal
Journal of Biomedical Science
Journal Volume
20
Journal Issue
1
Pages
39
Date Issued
2013
Author(s)
Abstract
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.
Other Subjects
gelatinase B; mitogen activated protein kinase p38; placental growth factor; vasculotropin receptor 1; FLT1 protein, human; gelatinase B; mitogen activated protein kinase p38; placenta protein; placental growth factor; vasculotropin receptor 1; gelatinase B; mitogen activated protein kinase p38; placenta protein; vasculotropin receptor 1; advanced cancer; apoptosis; article; cancer prognosis; cell migration; colorectal cancer; enzyme activation; enzyme linked immunosorbent assay; human; human tissue; immunohistochemistry; priority journal; protein expression; reverse transcription polymerase chain reaction; signal transduction; tumor invasion; tumor xenograft; cell proliferation; colorectal tumor; female; genetics; metabolism; pathology; phosphorylation; tumor cell line; colorectal tumor; metabolism; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Female; Humans; Matrix Metalloproteinase 9; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pregnancy Proteins; Signal Transduction; Vascular Endothelial Growth Factor Receptor-1; Apoptosis; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Female; Humans; Matrix Metalloproteinase 9; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pregnancy Proteins; Signal Transduction; Vascular Endothelial Growth Factor Receptor-1
Type
journal article