title: Matrix metalloproteinase-9 silencing by RNA interference promotes the adhesive-invasive switch in HT1080 human fibrosarcoma cells.
abstract: BACKGROUND
  A high level of matrix metalloproteinase-9 (MMP-9) is associated with human tumor invasion and/or metastasis. The HT1080 human fibrosarcoma cell line is highly invasive and metastatic which constitutively express MMP-9.
  
  
  METHODS
  HT1080 cells transfected with a double stranded RNA that targeted the MMP-9 mRNA and the cellular characteristics were examined before and after interference. The inhibition effects of MMP-9 interference on the tumor growth of HT1080 cells in nude mice was also tested by xenograft assay.
  
  
  RESULTS
  MMP-9 extinction in HT1080 resulted in the following: (1) inhibited cell mobility; (2) increased cell adhesion, and (3) attenuated tumor cell migration. In addition, MMP-9 knockdown concomitantly resulted in decreased levels of soluble ICAM-1, leading to an adhesion defect and tumor metastasis. Moreover, in vivo assay further demonstrated MMP-9 interference affecting the tumorigenesis of HT1080 cells in mice as follows (1) inhibition of tumor growth; (2) reduced tumor volume, and (3) prolonged survival time.
  
  
  CONCLUSIONS
  Our observations defined a novel critical role for MMP-9 in the progression of HT1080 fibrosarcoma by changing the inter-cellular adhesion molecular-1 from membrane-anchored state to a soluble one which provides a target for promising tumor therapy in clinics.
authors.affiliation: Institute of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University (The 9th hospital of Peking University), Beijing 100038, PR China. zhuxishan@tsinghua.org.cn
authors.forename: Xishan
authors.initials: X
authors.lastname: Zhu
authors.forename: Weiping
authors.initials: W
authors.lastname: Tai
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Song
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Guangyu
authors.initials: G
authors.lastname: An
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005354:Fibrosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020868:Gene Silencing; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009362:Neoplasm Metastasis; D034622:RNA Interference
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9