title: Pigment epithelium-derived factor upregulates collagen I and downregulates matrix metalloproteinase 2 in osteosarcoma cells, and colocalises to collagen I and heat shock protein 47 in fetal and adult bone.
abstract: OBJECTIVE
  Pigment epithelium-derived factor (PEDF) has proven anti-osteosarcoma activity. However, the mechanism(s) underpinning its ability to reduce primary bone tumour (osteosarcoma) metastasis is unknown.
  
  
  METHODS
  Adult and fetal murine bone were immunostained for PEDF, collagen I (major protein in bone) and its processing proteins, heat shock protein 47 (HSP47, a chaperone protein for collagen I), membrane type I matrix metalloproteinase (MT1-MMP, a collagenase), and matrix metalloproteinase 2 (MMP-2, which is activated by MT1-MMP). Immunoblotting and immunocytochemistry were used to observe levels of the above biomarkers when human osteosarcoma cells were treated with PEDF.
  
  
  RESULTS
  Immunohistochemical staining in adult and fetal bone mirrors collagen I. PEDF localised to ridges of trabecular bone in tibial cortex and to megakaryocytes within bone marrow. Second, we observed that PEDF upregulates collagen I, HSP47 and MT1-MMP, while downregulating MMP-2 in osteosarcoma cells in vitro.
  
  
  CONCLUSIONS
  PEDF is a promising antagonist to osteosarcoma cell metastasis via downregulation of MMP-2, and can induce tumour cells to further adopt differentiative properties, thereby possibly reducing their aggressive growth in vitro and in vivo.
authors.affiliation: College of Health and Biomedicine, Victoria University, St Albans, Australia.
authors.forename: Marice B
authors.initials: MB
authors.lastname: Alcantara
authors.forename: Natalie
authors.initials: N
authors.lastname: Nemazannikova
authors.forename: Mina
authors.initials: M
authors.lastname: Elahy
authors.forename: Crispin R
authors.initials: CR
authors.lastname: Dass
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism*; D015536:Down-Regulation; D005136:Eye Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005333:Fetus; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D024042:Collagen Type I; D005136:Eye Proteins; D050958:HSP47 Heat-Shock Proteins; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: bone; cancer; collagen I; matrix metalloproteinase; pigment epithelium-derived factor