title: Novel enhanced lung-colonizing variant of murine MBT-2 bladder cancer cells.
abstract: OBJECTIVE
  To develop an enhanced lung-colonizing variant of murine bladder cancer that will allow the mechanism of metastasis to be studied more readily.
  
  
  METHODS
  We implanted murine bladder tumor cells (MBT-2) into the leg muscles of C3H mice. We developed variant cells from a lung metastasis nodule. We compared the MBT-2 cells and variant cells (MBT-2V) in vivo by evaluating lung nodule formation, survival, in vitro adhesion, and migration-invasion assays. Zymography and semiquantitative reverse transcriptase-polymerase chain reaction analyses were also performed to characterize the metastatic ability of both cells.
  
  
  RESULTS
  MBT-2 and MBT-2V cells were tumorigenic when injected intramuscularly into C3H mice, but MBT-2 cells had little potential to metastasize compared with MBT-2V cells. Metastases were observed in the lungs of mice injected in the tail vein with MBT-2 and MBT-2V cells. Mice receiving MBT-2V cells had significantly shorter survival (P <0.01) and more lung nodules (245 versus 106, P <0.0001) than those receiving MBT-2 cells. In vitro study revealed that MBT-2V cells exhibited more adhesion, greater migration, and more invasiveness than did MBT-2 cells. Pathologic examination revealed the tumors from MBT-2V cells to be more aggressive than those from MBT-2 cells. MBT-2V also showed significantly greater matrix metalloproteinase-9 expression.
  
  
  CONCLUSIONS
  We generated an enhanced lung-colonizing variant of MBT-2 cells. Our MBT-2V cells showed more aggressive and invasive metastatic ability than that of the MBT-2 cells. Zymography and reverse transcriptase-polymerase chain reaction analyses indicated that matrix metalloproteinase-9 might be associated with the metastatic ability of MBT-2V cells.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. m5508985@ra2.so-net.ne.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Horinaga
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Fukuyama
authors.forename: Toru
authors.initials: T
authors.lastname: Nishiyama
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Harsch
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Cicek
authors.forename: Warren
authors.initials: W
authors.lastname: Heston
authors.forename: Nywana
authors.initials: N
authors.lastname: Sizemore
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: William
authors.initials: W
authors.lastname: Larchian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D009374:Neoplasms, Experimental / Q000556:secondary*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*