國家衛生研究院 NHRI:Item 3990099045/3044
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 856518      Online Users : 666
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3044


    Title: Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis
    Authors: Chang, CC;Shih, JY;Jeng, YM;Su, JL;Lin, BZ;Chen, ST;Chau, YP;Yang, PC;Kuo, ML
    Contributors: National Institute of Cancer Research
    Abstract: Background: Tumor invasion and metastasis cause most deaths in cancer patients. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells, but few mechanistic details are known. We investigated the roles of CTGF and collapsin response mediator protein 1 (CRMP-1) in metastasis and invasion of human lung adenocarcinoma. Methods: We compared vector control-transfected cells with corresponding CTGF gene-transfected cells. Invasive activity was measured with a modified Boyden chamber assay, and metastatic activity was measured in an animal model. We used CTGF deletion mutants, CTGF and CRMP-I antisense oligonucleotides, and anti-integrin and anti-CRMP-1 antibodies to investigate the functional relationship between CTGF and CRMP-1. Expression of CTGF protein in 78 lung adenocarcinoma specimens was investigated immunohistochemically. All statistical tests were two-sided. Results: Invasive (both P<.001) and metastatic (P<.001 and P = .003, respectively) activities were lower in cells that overexpress CTGF than in vector control cells. Expression of CRMP-1 was higher in CTGF-transfected clones than in vector control cells, and its level decreased after cells were treated with anti-integrin alpha(v)beta(3) and alpha(v)beta(5) antibodies. Reduced levels of CRMP-I protein after the transfection of CRMP-1-specific antisense oligonucleotides, but not sense oligonucleotides, increased the invasiveness of CTGF-transfected cells (mean numbers of invasive CTGF-transfected cells treated with 20 muM CRMP-1-specific sense and antisense oligonucleotides were 327 and 516 cells, respectively [difference = 189 cells, 95% confidence interval {CI} = 156 to 221 cells; P<.001]). The CT module of CTGF was the region primarily responsible for the increased expression of CRNIP-I and the inhibition of invasion (mean numbers of invasive cells expressing full-length CTGF and CT module-deleted mutant were 148 and 385 cells, respectively [difference = 237 cells, 95% CI = 208 to 266 cells; P<.0011). Reduced expression of CTGF in lung cancer specimens was statistically significantly associated with the risk of more advanced-stage disease (stages III and IV versus stages I and 11; P = .001), lymph node metastasis (P = .014), and shorter survival (median survival with high levels of CTGF = 66.7 months and median survival for low levels = 18.2 months; difference = 48.5 months, 95% CI = 33.5 to 63.5 months; P = .02). Conclusion: CTGF inhibits metastasis and invasion of human lung adenocarcinoma by a CRMP-1-dependent mechanism.
    Keywords: Oncology
    Date: 2004-03-03
    Relation: Journal of the National Cancer Institute. 2004 Mar;96(5):364-375.
    Link to: http://dx.doi.org/10.1093/jnci/djh059
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8874&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000220090500009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=1542288151
    Appears in Collections:[Others] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    000220090500009.pdf488KbAdobe PDF589View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback