• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    A PSP94-derived peptide PCK3145 inhibits MMP-9 secretion and triggers CD44 cell surface shedding: implication in tumor metastasis.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Annabi, Borhane
    Bouzeghrane, Mounia
    Currie, Jean-Christophe
    Hawkins, Robert E
    Dulude, Hélène
    Daigneault, Luc
    Ruiz, Marcia
    Wisniewski, Jan
    Garde, Seema
    Rabbani, Shafaat A
    Panchal, Chandra
    Wu, Jinzi J
    Béliveau, Richard
    Show allShow less
    Affiliation
    Laboratoire d'Oncologie Moléculaire, Département de Chimie-Biochimie, Université du Québec à Montréal, Montreal, Quebec, Canada.
    Issue Date
    2005
    
    Metadata
    Show full item record
    Abstract
    PURPOSE: PCK3145 is a synthetic peptide corresponding to amino acids 31-45 of prostate secretory protein 94, which can reduce experimental skeletal metastases and prostate tumor growth in vivo. Part of its biological action involves the reduction of circulating plasma matrix metalloproteinase (MMP)-9, a crucial mediator in extracellular matrix (ECM) degradation during tumor metastasis and cancer cell invasion. The antimetastatic mechanism of action of PCK3145 is however, not understood. EXPERIMENTAL DESIGN: HT-1080 fibrosarcoma cells were treated with PCK3145, and cell lysates used for immunoblot analysis of small GTPase RhoA and membrane type (MT)1-MMP protein expression. Conditioned media was used to monitor soluble MMP-9 gelatinolytic activity by zymography and protein expression by immunoblotting. RT-PCR was used to assess RhoA, MT1-MMP, MMP-9, RECK, and CD44 gene expression. Flow cytometry was used to monitor cell surface expression of CD44 and of membrane-bound MMP-9. Cell adhesion was performed on different purified ECM proteins, while cell migration was specifically performed on hyaluronic acid (HA). RESULTS: We found that PCK3145 inhibited HT-1080 cell adhesion onto HA, laminin-1, and type-I collagen suggesting the common implication of the cell surface receptor CD44. In fact, PCK3145 triggered the shedding of CD44 from the cell surface into the conditioned media. PCK3145 also inhibited MMP-9 secretion and binding to the cell surface. This effect was correlated to increased RhoA and MT1-MMP gene and protein expression. CONCLUSIONS: Our data suggest that PCK3145 may antagonize tumor cell metastatic processes by inhibiting both MMP-9 secretion and its potential binding to its cell surface docking receptor CD44. Such mechanism may involve RhoA signaling and increase in MT1-MMP-mediated CD44 shedding. Together with its beneficial effects in clinical trials, this is the first demonstration of PCK3145 acting as a MMP secretion inhibitor.
    Citation
    A PSP94-derived peptide PCK3145 inhibits MMP-9 secretion and triggers CD44 cell surface shedding: implication in tumor metastasis. 2005, 22 (5):429-39 Clin. Exp. Metastasis
    Journal
    Clinical & Experimental Metastasis
    URI
    http://hdl.handle.net/10541/76275
    DOI
    10.1007/s10585-005-2669-1
    PubMed ID
    16283486
    Type
    Article
    Language
    en
    ISSN
    0262-0898
    ae974a485f413a2113503eed53cd6c53
    10.1007/s10585-005-2669-1
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Inhibition of MMP-9 secretion by the anti-metastatic PSP94-derived peptide PCK3145 requires cell surface laminin receptor signaling.
    • Authors: Annabi B, Bouzeghrane M, Currie JC, Dulude H, Daigneault L, Garde S, Rabbani SA, Panchal C, Wu JJ, Béliveau R
    • Issue date: 2006 Apr
    • A prostate secretory protein94-derived synthetic peptide PCK3145 inhibits VEGF signalling in endothelial cells: implication in tumor angiogenesis.
    • Authors: Lamy S, Ruiz MT, Wisniewski J, Garde S, Rabbani SA, Panchal C, Wu JJ, Annabi B
    • Issue date: 2006 May 1
    • Probing the infiltrating character of brain tumors: inhibition of RhoA/ROK-mediated CD44 cell surface shedding from glioma cells by the green tea catechin EGCg.
    • Authors: Annabi B, Bouzeghrane M, Moumdjian R, Moghrabi A, Béliveau R
    • Issue date: 2005 Aug
    • Contribution of the 37-kDa laminin receptor precursor in the anti-metastatic PSP94-derived peptide PCK3145 cell surface binding.
    • Authors: Annabi B, Currie JC, Bouzeghrane M, Dulude H, Daigneault L, Garde S, Rabbani SA, Panchal C, Wu JJ, Béliveau R
    • Issue date: 2006 Jul 21
    • Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells.
    • Authors: Desai B, Rogers MJ, Chellaiah MA
    • Issue date: 2007 Mar 7
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.