title: Connective tissue growth factor inhibits metastasis and acts as an independent prognostic marker in colorectal cancer.
abstract: OBJECTIVE
  Connective tissue growth factor (CTGF) has been shown to be implicated in tumor development and progression. The aim of this study was to investigate the role of CTGF in progression of colorectal cancer (CRC).
  
  
  METHODS
  Immunohistochemical staining of specimens from 119 patients with CRC was performed. Liposome-mediated transfection was used to introduce a CTGF expression vector into CRC cell lines. Transfectants were tested in invasive ability and experimental hepatic metastasis in BALB/c mice. Furthermore, a FOPflash/TOPflash reporter assay was performed to investigate CTGF on the beta-catenin/T-cell factor signaling pathway.
  
  
  RESULTS
  Patients with stage II and stage III CRC whose tumors displayed high CTGF expression had a significantly higher overall survival and a disease-free advantage over patients with CRC with low CTGF expression. Alterations in the CTGF level in CRC cell lines modulated their invasive ability with an inverse correlation. In addition, a reduction in the CTGF level of CT26 cells after stable transfection with antisense CTGF resulted in increased liver metastasis in BALB/c mice. The activity of the beta-catenin/T-cell factor signaling pathway and its downstream effector gene matrix metalloproteinase 7 in these CTGF-transfected cells was strongly attenuated. Blockage of matrix metalloproteinase 7 with its neutralizing antibodies inhibited increased invasiveness in antisense CTGF-transfected CT26 cells.
  
  
  CONCLUSIONS
  Our results implicate CTGF as a key regulator of CRC invasion and metastasis, and it appears to be a useful and better prognosis factor for patients with stage II and stage III CRC.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Been-Ren
authors.initials: BR
authors.lastname: Lin
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chang
authors.forename: Ting-Fang
authors.initials: TF
authors.lastname: Che
authors.forename: Szu-Ta
authors.initials: ST
authors.lastname: Chen
authors.forename: Robert Jeen-Chen
authors.initials: RJ
authors.lastname: Chen
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Jin-Tung
authors.initials: JT
authors.lastname: Liang
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Yat-Pang
authors.initials: YP
authors.lastname: Chau
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D055513:Connective Tissue Growth Factor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D023421:Models, Animal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051176:beta Catenin; D055513:Connective Tissue Growth Factor