title: p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer.
abstract: The p75 neurotrophin receptor (p75NTR) is a focus for study at present. However, its function in gastric cancer was not elucidated. Here, we investigated its relation with metastasis of gastric cancer. By immunohistochemistry, we found that the positive rate of p75NTR expression in metastatic gastric cancer was 15.09% (16 of 106), which was lower compared with nonmetastatic gastric cancer (64.15%; 68 of 106). The average staining score in nonmetastatic gastric cancer was significantly higher than in metastatic gastric cancer (1.21 +/- 0.35 versus 0.23 +/- 0.18; P<0.01). p75NTR protein level was also lowly expressed in the highly liver-metastatic gastric cancer cell line XGC9811-L compared with other gastric cancer cell lines by Western blotting. It could also significantly inhibit the in vitro adhesive, invasive, and migratory and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45 by reducing urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 proteins and by increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein. Further studies showed that p75NTR could suppress the nuclear factor-kappaB (NF-kappaB) signal. SN50, a specific inhibitor of NF-kappaB, which could inhibit in vitro invasive and migratory abilities of gastric cancer cells, reduced expression of uPA and MMP9 proteins and increased expression of TIMP1 protein. Taken together, p75NTR had the function of inhibiting the invasive and metastatic abilities of gastric cancer cells, which was mediated, at least partially, by down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein via the NF-kappaB signal transduction pathway. Our studies suggested that p75NTR may be used as a new potential therapeutic target in metastatic gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, 17 Changle Western Road, Xi'an 710032, Shaanxi Province, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.forename: Yanglin
authors.initials: Y
authors.lastname: Pan
authors.forename: Lijie
authors.initials: L
authors.lastname: He
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Jiugang
authors.initials: J
authors.lastname: Song
authors.forename: Huahong
authors.initials: H
authors.lastname: Xie
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.forename: Shuang
authors.initials: S
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; D020800:Receptor, Nerve Growth Factor; D019715:Tissue Inhibitor of Metalloproteinase-1; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9