title: Monitoring dynamic interactions between breast cancer cells and human bone tissue in a co-culture model.
abstract: OBJECTIVE
  Bone is a preferential site of breast cancer metastasis, and models are needed to study this process at the level of the microenvironment. We have used bioluminescence imaging (BLI) and multiplex biomarker immunoassays to monitor dynamic breast cancer cell behaviors in co-culture with human bone tissue.
  
  
  METHODS
  Femur tissue fragments harvested from hip replacement surgeries were co-cultured with luciferase-positive MDA-MB-231-fLuc cells. BLI was performed to quantify breast cell proliferation and track migration relative to bone tissue. Breast cell colonization of bone tissues was assessed with immunohistochemistry. Biomarkers in co-culture supernatants were profiled with MILLIPLEX(®) immunoassays.
  
  
  RESULTS
  BLI demonstrated increased MDA-MB-231-fLuc cell proliferation (p < 0.001) in the presence vs. absence of bones and revealed breast cell migration toward bone. Immunohistochemistry illustrated MDA-MB-231-fLuc cell colonization of bone, and MILLIPLEX(®) profiles of culture supernatants suggested breast/bone crosstalk.
  
  
  CONCLUSIONS
  Breast cell behaviors that facilitate metastasis occur reproducibly in human bone tissue co-cultures and can be monitored and quantified using BLI and multiplex immunoassays.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, 150E Clark Center, 318 Campus Drive, Stanford, CA, 94305-5427, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Lie
authors.forename: Marie C
authors.initials: MC
authors.lastname: Bammer
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Hardy
authors.forename: Tobi L
authors.initials: TL
authors.lastname: Schmidt
authors.forename: William J
authors.initials: WJ
authors.lastname: Maloney
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: King
mesh_terms: D019644:Arthroplasty, Replacement, Hip; D014408:Biomarkers, Tumor / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D008954:Models, Biological; D057054:Molecular Imaging
chemical_list: D014408:Biomarkers, Tumor; D008156:Luciferases