title: A novel brain metastases model developed in immunodeficient rats closely mimics the growth of metastatic brain tumours in patients.
abstract: OBJECTIVE
  brain metastasis is a common cause of mortality in cancer patients, and associated with poor prognosis. Our objective was to develop a clinically relevant animal model by transplanting human biopsy spheroids derived from metastatic lesions into brains of immunodeficient rats.
  
  
  METHODS
  nine different patient brain metastases from four different primary cancers were implanted into brains of immunodeficient rats. The xenografts were compared with patient tumours by magnetic resonance imaging, histochemistry, immunohistochemistry and DNA copy number analysis.
  
  
  RESULTS
  after transplantation, tumour growth was achieved in seven out of nine human brain metastases. Spheroids derived from four of the metastases initiated in the rat brains were further serially transplanted into new animals and a 100% tumour take was observed during second passage. Three of the biopsies were implanted subcutaneously, where no tumour take was observed. The animal brain metastases exhibited similar radiological features as observed clinically. Histological comparisons between the primary tumours from the patients, the patient brain metastases and the derived xenografts showed striking similarities in histology and growth patterns. Also, immunohistochemistry showed a strong marker expression similarity between the patient tumours and the corresponding xenografts. DNA copy number analysis between the brain metastases, and the corresponding xenografts revealed strong similarities in gains and losses of chromosomal content.
  
  
  CONCLUSIONS
  we have developed a representative in vivo model for studying the growth of human metastatic brain cancers. The model described represents an important tool to assess responses to new treatment modalities and for studying mechanisms behind metastatic growth in the central nervous system.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: Daphu
authors.forename: P-H
authors.initials: PH
authors.lastname: Pedersen
authors.forename: H
authors.initials: H
authors.lastname: Miletic
authors.forename: R
authors.initials: R
authors.lastname: Hovland
authors.forename: S
authors.initials: S
authors.lastname: Mørk
authors.forename: R
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: C
authors.initials: C
authors.lastname: Tiron
authors.forename: E
authors.initials: E
authors.lastname: McCormack
authors.forename: D
authors.initials: D
authors.lastname: Micklem
authors.forename: J B
authors.initials: JB
authors.lastname: Lorens
authors.forename: H
authors.initials: H
authors.lastname: Immervoll
authors.forename: F
authors.initials: F
authors.lastname: Thorsen
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D004195:Disease Models, Animal; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays