title: Esophageal cancer stem cells express PLGF to increase cancer invasion through MMP9 activation.
abstract: Cancer stem cells (CSCs) are a distinct population in tumors and cause cancer relapse and metastasis. Thus, treating CSCs are believed to be potential to cure rapidly growing and highly metastatic cancers. To date, CSCs in esophageal cancer have not been characterized. In the current study, we detected significant higher levels of placental growth factor (PLGF) and matrix metalloproteinase 9 (MMP9) in the esophageal cancers with metastasis, compared to those without metastasis, in which the expression levels of PLGF and MMP9 strongly correlated with each other. Thus, we used a human esophageal cancer cell line, TE-1, to examine the cross talk of PLGF and MMP9. We found that the levels of PLGF in TE-1 cells positively affected the levels of MMP9, while the levels of MMP9 did not affected the levels of PLGF, suggesting that PLGF may activate MMP9 in esophageal cancer cells. Then, we separated PLGF-positive and PLGF-negative TE-1 cells that had been transfected with a GFP reporter under a PLGF promoter by flow cytometry. We found that PLGF-positive cells grew significantly faster than PLGF-negative cells both in vitro and in vivo in a stereotactical implantation model, suggesting that PLGF-positive cells are likely CSCs in esophageal cancer. Taken together, we demonstrate that PLGF-positive cells appear to be CSCs in esophageal cancer, and they may release PLGF to promote cancer metastasis through MMP9 activation.
authors.affiliation: Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai, 200127, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Tinghui
authors.initials: T
authors.lastname: Jiang
authors.forename: Aiwu
authors.initials: A
authors.lastname: Mao
authors.forename: Jianrong
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D057054:Molecular Imaging; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D020780:Matrix Metalloproteinase 9