title: Development of metastatic and non-metastatic tumor lines from a patient's prostate cancer specimen-identification of a small subpopulation with metastatic potential in the primary tumor.
abstract: BACKGROUND
  Metastasis is the major cause of prostate cancer deaths. Tumor heterogeneity in both primary and metastatic prostate cancers is a major hurdle in elucidating the mechanisms of metastasis in this disease. To circumvent this obstacle and improve our understanding of prostate cancer metastasis, we developed multiple tumor tissue lines from one patient's primary prostate cancer specimen to examine differences in metastatic ability.
  
  
  METHODS
  Pieces of tissue from different foci of a patient's primary prostate tumor were grafted into subrenal capsules of NOD-SCID mice and transplantable tumor sublines were established by serial passage. The metastatic ability of each subline was tested via orthotopic grafting into mice. Chromosomal alterations exclusively presented in a metastatic subline were examined by SKY and investigated for their presence in parental tissues by fluorescence in situ hybridization.
  
  
  RESULTS
  Three transplantable sublines were developed, resembling the primary tumor histologically, exhibiting poor differentiation, and different growth rates. Importantly, the LTL-220N and LTL-221N sublines were non-metastatic, whereas the LTL-220M subline was spontaneously metastatic in vivo. SKY analysis showed limited but unique chromosomal alterations in each subline. Some chromosomal alterations, exclusively present in the metastatic LTL-220M subline, were also observed in a small portion of the parental cancer tissues.
  
  
  CONCLUSIONS
  The results indicate that in primary prostate tumors metastatic potential can be confined to a minority of cancer cells. Subrenal capsule xenograft methodology can be used to dissect heterogeneous cancer cells in a patient's primary tumor and sublines derived from such cells provide valuable tools for investigating mechanisms underlying prostate cancer metastasis.
authors.affiliation: Department of Cancer Endocrinology, BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Jane
authors.initials: J
authors.lastname: Bayani
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.forename: Marianne D
authors.initials: MD
authors.lastname: Sadar
authors.forename: Maisa
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D032681:Spectral Karyotyping; D014183:Transplantation, Heterologous