title: Human desmoid fibroblasts: matrix metalloproteinases, their inhibitors and modulation by Toremifene.
abstract: BACKGROUND
  Desmoid tumour is a benign, non metastasising neoplasm characterised by an elevated deposition of organic macromolecules in the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of ECM macromolecules. The MMPs and their natural inhibitors (TIMPs) have been implicated in tumour growth, invasion and metastasis. In this study we provide evidence that the in vitro cultured cell line from desmoid tumour accumulates more collagen fibres in the ECM than healthy fibroblasts.
  
  
  METHODS
  We investigated collagen accumulation by 3H-thymidine incorporation, MMP expression by substrate gel zymography and TIMP expression by Western blot analysis.
  
  
  RESULTS
  Desmoid fibroblasts showed a reduction in MMP activity and an increase of type I and III collagen and TIMPs compared to normal fibroblasts.
  
  
  CONCLUSIONS
  The increase in collagen in desmoid fibroblasts was due to inhibited collagen degradation (reduction of MMP activity) rather than to increased collagen synthesis. Adding toremifene, an anti-estrogen triphenylethylene derivate, to desmoid fibroblasts reduced collagen accumulation by decreasing mRNA expression and increasing collagen degradation.
authors.affiliation: Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy. chiara.balducci@tiscali.it <chiara.balducci@tiscali.it>
authors.forename: Chiara
authors.initials: C
authors.lastname: Balducci
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lilli
authors.forename: Giordano
authors.initials: G
authors.lastname: Stabellini
authors.forename: Lorella
authors.initials: L
authors.lastname: Marinucci
authors.forename: Giammario
authors.initials: G
authors.lastname: Giustozzi
authors.forename: Alessio
authors.initials: A
authors.lastname: Becchetti
authors.forename: Lucio
authors.initials: L
authors.lastname: Cagini
authors.forename: Paola
authors.initials: P
authors.lastname: Locci
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D003094:Collagen / Q000032:analysis*; D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D018222:Desmoid Tumors / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D011347:Procollagen / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D018931:Antineoplastic Agents, Hormonal; D061965:Matrix Metalloproteinase Inhibitors; D011347:Procollagen; D019714:Tissue Inhibitor of Metalloproteinases; D017312:Toremifene; D003094:Collagen; D017364:Collagenases; D020782:Matrix Metalloproteinases
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