title: Bone invading NSCLC cells produce IL-7: mice model and human histologic data.
abstract: BACKGROUND
  Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.
  
  
  METHODS
  We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.
  
  
  RESULTS
  At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.
  
  
  CONCLUSIONS
  We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.
authors.affiliation: CeRMS (Center for Experimental Research and Medical Studies) University of Turin and A,O,U, San Giovanni Battista, Turin, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Roato
authors.forename: Davide
authors.initials: D
authors.lastname: Caldo
authors.forename: Laura
authors.initials: L
authors.lastname: Godio
authors.forename: Lucia
authors.initials: L
authors.lastname: D'Amico
authors.forename: Paolo
authors.initials: P
authors.lastname: Giannoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morello
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Quarto
authors.forename: Luigi
authors.initials: L
authors.lastname: Molfetta
authors.forename: Paolo
authors.initials: P
authors.lastname: Buracco
authors.forename: Antonio
authors.initials: A
authors.lastname: Mussa
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferracini
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis
chemical_list: D015851:Interleukin-7