Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway
Copyright policy )Flt-1 in colorectal cancer cells is required for the tumor invasive effect of placental growth factor through a p38-MMP9 pathway
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.
- National Taiwan University of Arts Taiwan
- Massachusetts General Hospital United States
- National Taiwan University Hospital Taiwan
- Harvard University United States
- Memorial Hospital of South Bend United States
Biochemistry, medical, Vascular Endothelial Growth Factor Receptor-1, Endocrinology, Diabetes and Metabolism, Research, Clinical Biochemistry, Apoptosis, Cell Biology, Pregnancy Proteins, p38 Mitogen-Activated Protein Kinases, Matrix Metalloproteinase 9, Cell Line, Tumor, Humans, Pharmacology (medical), Female, Phosphorylation, Colorectal Neoplasms, Molecular Biology, Cell Proliferation, Placenta Growth Factor, Signal Transduction
Biochemistry, medical, Vascular Endothelial Growth Factor Receptor-1, Endocrinology, Diabetes and Metabolism, Research, Clinical Biochemistry, Apoptosis, Cell Biology, Pregnancy Proteins, p38 Mitogen-Activated Protein Kinases, Matrix Metalloproteinase 9, Cell Line, Tumor, Humans, Pharmacology (medical), Female, Phosphorylation, Colorectal Neoplasms, Molecular Biology, Cell Proliferation, Placenta Growth Factor, Signal Transduction
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