title: Interleukin-1 alpha and basic fibroblast growth factor induction of matrix metalloproteinases and their inhibitors in osteosarcoma cells is modulated by the metastasis associated protein CAPL.
abstract: BACKGROUND
  Several recent investigations have shown that the expression of the CAPL protein seems to be of importance in the metastatic potential in some types of cancer. However, the mechanisms behind this and other biological functions of CAPL are still largely unknown. The aim of the present work was to investigate whether CAPL could affect the expression of candidate proteolytic facilitators of the metastatic process, i.e. matrix metalloproteinases (MMPs) and their inhibitors (TIMPs).
  
  
  METHODS
  A highly metastatic osteosarcoma cell-line with a high expression of CAPL was transfected with either a vector containing a ribozyme against this transcript, or with the vector alone as a control. The expression of MMPs and TIMPs was investigated with ELISA and gelatin zymography.
  
  
  RESULTS
  The cell-line with a low CAPL expression (III-14) responded to bFGF treatment by an increased synthesis of MMP-1 and MMP-9 and to Il-1 alpha treatment by an increased synthesis of MMP-9. In contrast, the cell-line with a high CAPL expression (pH beta-1) did not respond with an altered expression of these MMPs. Neither of these two cell-lines responded with an altered expression of MMP-2. bFGF treatment resulted in an increased expression of TIMP-1 in both cell-lines, while Il-1 alpha treatment resulted in a decreased production of TIMP-1 in pH beta-1 cells, and III-14 cells were unaffected.
  
  
  CONCLUSIONS
  The CAPL protein expressed in cell-cultures appear to block the MMP induction by bFGF and Il-1 alpha. However, the induction of TIMP-1 by bFGF must proceed through a pathway different from the MMP induced pathway, i.e. a pathway unaffected by CAPL. In addition, CAPL appeared to act in synergy with Il-1 alpha to reduce the synthesis of TIMP-1.
authors.affiliation: Department of Biochemistry, Institute of Medical Biology, Tromsø, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Andersen
authors.forename: G M
authors.initials: GM
authors.lastname: Maelandsmo
authors.forename: E
authors.initials: E
authors.lastname: Hovig
authors.forename: O
authors.initials: O
authors.lastname: Fodstad
authors.forename: T
authors.initials: T
authors.lastname: Loennechen
authors.forename: J O
authors.initials: JO
authors.lastname: Winberg
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D004790:Enzyme Induction; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism* / Q000556:secondary; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D016222:Fibroblast Growth Factor 2; C077591:S100A4 protein, human; D017364:Collagenases; D020781:Matrix Metalloproteinase 1