title: Potential establishment of lung metastatic xenograft model of androgen receptor-positive and androgen-independent prostate cancer (C4-2B).
abstract: OBJECTIVE
  To establish a mouse xenograft model of metastatic prostate cancer (PCa) and investigate the relationship between metastasis and circulating tumor cells.
  
  
  METHODS
  Flow cytometry (FACS) was used to detect suitable PCa cells and markers for detecting circulating tumor cells in vivo. We orthotopically injected androgen receptor-positive and androgen-independent C4-2B PCa cells into 12 severe combined immunodeficiency (SCID) mouse prostates, including 1 vehicle control. We measured the serum prostate-specific antigen levels biweekly after tumor inoculation. Circulating tumor cells (CTCs) were measured qualitatively by fluorescent microscopy immediately after the mice were sacrificed. The mouse prostates and lungs were examined for tumor formation using immunohistochemistry because we found no apparent metastasis, except in the lung.
  
  
  RESULTS
  FACS analyses in vitro identified the marker, prostate-specific membrane antigen, and C4-2B cells to be appropriate for additional in vivo study. We confirmed that the serum prostate-specific antigen increase was dependent on time and prostate tumor weight in mice. Of the 11 mice, 6 could be used as the mouse PCa xenograft model. Fluorescent microscopy detected CTCs in the peripheral blood in 5 of the 6 mice constituting the PCa model. Human prostate-specific antigen expression was detected by immunohistochemistry in the prostates of all the mice and in the lung of 2 of the 6 mice, suggesting 2 mice with lung metastasis.
  
  
  CONCLUSIONS
  We have shown the potential establishment of a mouse lung metastatic xenograft model of androgen receptor-positive and androgen-independent C4-2B PCa tumor. However, the present model requires improvement to be a more reproducible, accurate and complete experimental model. Additional study is necessary to verify the relationship between metastasis and CTCs.
authors.affiliation: Department of Urology, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Japan.
authors.forename: Fukashi
authors.initials: F
authors.lastname: Yamamichi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shigemura
authors.forename: Masato
authors.initials: M
authors.lastname: Kawabata
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009360:Neoplastic Cells, Circulating; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D000728:Androgens; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen