title: A short-term in vivo model for giant cell tumor of bone.
abstract: BACKGROUND
  Because of the lack of suitable in vivo models of giant cell tumor of bone (GCT), little is known about its underlying fundamental pro-tumoral events, such as tumor growth, invasion, angiogenesis and metastasis. There is no existing cell line that contains all the cell and tissue tumor components of GCT and thus in vitro testing of anti-tumor agents on GCT is not possible. In this study we have characterized a new method of growing a GCT tumor on a chick chorio-allantoic membrane (CAM) for this purpose.
  
  
  METHODS
  Fresh tumor tissue was obtained from 10 patients and homogenized. The suspension was grafted onto the CAM at day 10 of development. The growth process was monitored by daily observation and photo documentation using in vivo biomicroscopy. After 6 days, samples were fixed and further analyzed using standard histology (hematoxylin and eosin stains), Ki67 staining and fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  The suspension of all 10 patients formed solid tumors when grafted on the CAM. In vivo microscopy and standard histology revealed a rich vascularization of the tumors. The tumors were composed of the typical components of GCT, including (CD51+/CD68+) multinucleated giant cells which were generally less numerous and contained fewer nuclei than in the original tumors. Ki67 staining revealed a very low proliferation rate. The FISH demonstrated that the tumors were composed of human cells interspersed with chick-derived capillaries.
  
  
  CONCLUSIONS
  A reliable protocol for grafting of human GCT onto the chick chorio-allantoic membrane is established. This is the first in vivo model for giant cell tumors of bone which opens new perspectives to study this disease and to test new therapeutical agents.
authors.affiliation: Department of Trauma and Orthopedic Surgery, University of Witten-Herdecke, Cologne-Merheim Medical Center, Ostmerheimer Str, Cologne, Germany. maurice.balke@gmail.com
authors.forename: Maurice
authors.initials: M
authors.lastname: Balke
authors.forename: Anna
authors.initials: A
authors.lastname: Neumann
authors.forename: Károly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Konstantin
authors.initials: K
authors.lastname: Agelopoulos
authors.forename: Christian
authors.initials: C
authors.lastname: August
authors.forename: Georg
authors.initials: G
authors.lastname: Gosheger
authors.forename: Pancras Cw
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Nick
authors.initials: N
authors.lastname: Athanasou
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
authors.forename: Martin
authors.initials: M
authors.lastname: Hagedorn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000175:diagnosis / Q000473:pathology*; D002642:Chick Embryo; D004195:Disease Models, Animal; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult