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

Journal of Biomedical Science

Jau-Min Wong²  Zhifang Cao³  Meng-Tzu Weng⁴  Po-Nien Tsao¹  Shu-Chen Wei² 

[1] Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan;Departments of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan;Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA;Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei 100, Taiwan

关键词: MMP9;    Migration;    Invasion;    PlGF;    Flt-1;    Colorectal cancer;   

Others  :  823815
DOI  :  10.1186/1423-0127-20-39

 received in 2013-01-28, accepted in 2013-06-04,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Wei et al.; licensee BioMed Central Ltd.

【 图 表 】

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