title: Molecular pathways involved in crosstalk between cancer cells, osteoblasts and osteoclasts in the invasion of bone by oral squamous cell carcinoma.
abstract: OBJECTIVE
  This study investigates whether matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, interacting with other molecules important in osteoblast differentiation and osteoclastogenesis, could play important roles in the invasion of bone by oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  Supernatant (conditioned medium, CM) was collected from OSCC cell lines (SCC15 and SCC25), and from cultured osteoblasts (hFOB cell line and a primary culture, OB), and used for indirect co-culture: OSCC cells were treated with CM from osteoblasts and vice versa. Zymogenic activities of MMP-2 and -9, and protein quantities of all molecules studied, were detected by gelatine zymography and Western blotting, respectively. Real-time polymerase chain reaction (PCR) analysed mRNA of these molecules. Targeted molecules were examined by immunohistochemistry in tissue sections of bone-invasive OSCCs.
  
  
  RESULTS
  Zymogenic activities of both MMPs were increased in OSCC cells following culture with CM from hFOB: Twist1 protein expression was increased while Runx2 did not alter. The RANKL/OPG ratio, zymogen and protein expression of MMP-9 were increased in hFOB cells cultured with CM from OSCC lines, while zymogen expression of MMP-2 was decreased. Real-time PCR showed generally similar changes in expression of these molecules. All targeted molecules were expressed in invading malignant keratinocytes, and all but OPG were expressed in osteoclasts of clinical samples.
  
  
  CONCLUSIONS
  Crosstalk between different cell types appears to exist in the invasion of bone by OSCC. Understanding and ultimately interfering with the molecules involved may provide therapeutic approaches to inhibit such bone invasion.
authors.affiliation: Schools of Dentistry, Griffith University, Queensland, Australia.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Quan
authors.forename: Chuanxiang
authors.initials: C
authors.lastname: Zhou
authors.forename: Newell W
authors.initials: NW
authors.lastname: Johnson
authors.forename: Glenn
authors.initials: G
authors.lastname: Francis
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dahlstrom
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; D009687:Nuclear Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C493709:RUNX2 protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9