title: A novel 3-D mineralized tumor model to study breast cancer bone metastasis.
abstract: BACKGROUND
  Metastatic bone disease is a frequent cause of morbidity in patients with advanced breast cancer, but the role of the bone mineral hydroxyapatite (HA) in this process remains unclear. We have developed a novel mineralized 3-D tumor model and have employed this culture system to systematically investigate the pro-metastatic role of HA under physiologically relevant conditions in vitro.
  
  
  RESULTS
  MDA-MB231 breast cancer cells were cultured within non-mineralized or mineralized polymeric scaffolds fabricated by a gas foaming-particulate leaching technique. Tumor cell adhesion, proliferation, and secretion of pro-osteoclastic interleukin-8 (IL-8) was increased in mineralized tumor models as compared to non-mineralized tumor models, and IL-8 secretion was more pronounced for bone-specific MDA-MB231 subpopulations relative to lung-specific breast cancer cells. These differences were pathologically significant as conditioned media collected from mineralized tumor models promoted osteoclastogenesis in an IL-8 dependent manner. Finally, drug testing and signaling studies with transforming growth factor beta (TGFbeta) confirmed the clinical relevance of our culture system and revealed that breast cancer cell behavior is broadly affected by HA.
  
  
  CONCLUSIONS
  Our results indicate that HA promotes features associated with the neoplastic and metastatic growth of breast carcinoma cells in bone and that IL-8 may play an important role in this process. The developed mineralized tumor models may help to reveal the underlying cellular and molecular mechanisms that may ultimately enable more efficacious therapy of patients with advanced breast cancer.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
authors.forename: Siddharth P
authors.initials: SP
authors.lastname: Pathi
authors.forename: Christine
authors.initials: C
authors.lastname: Kowalczewski
authors.forename: Ramya
authors.initials: R
authors.lastname: Tadipatri
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischbach
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D002113:Calcification, Physiologic; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D017886:Durapatite / Q000378:metabolism; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008855:Microscopy, Electron, Scanning
chemical_list: D017077:Culture Media, Conditioned; D017886:Durapatite