title: In vivo selection of high-metastatic subline of bladder cancer cell and its characterization.
abstract: The majority of deaths associated with solid tumors are caused by tumor metastasis. To prevent metastasis, it is vital to understand its detailed process. In hematogenous metastasis of bladder cancer, some cancer cells disseminating into blood circulation extravasate into the lung tissues to form metastases. To study the molecular basis of the lung metastasis of bladder cancer, we employed an in vivo selection system that mimics hematogenous metastasis of bladder cancer on a low-metastatic bladder cancer cell line (KK-47). We have successfully isolated a high-metastatic bladder cancer subline, KK-47HM4, from KK-47 cells. We characterized KK-47HM4 in in vitro experimental systems. No significant difference in growth rate and susceptibility to NK cell attack between KK-47 and KK-47HM4 cells was observed. However, KK-47HM4 exhibited the higher capacities of Matrigel Matrix invasion and transendothelial invasion than KK-47. These results suggest that the extravasation of KK-47HM4 cells was enhanced among the multiple steps of the lung metastasis of bladder cancer. Our cDNA microarray analysis identified 67 genes whose expression was up- or downregulated in KK-47HM4 cells compared with KK-47 cells. This analysis data implied that one possible cause for enhanced extravasation of KK-47HM4 is its higher adhesion to extracellular matrix proteins. KK-47HM4 is the first bladder cancer subline with enhanced extravasation potential using the in vivo selection system. The information provided by our cDNA microarray analysis using KK-47HM4 will be useful for further investigation into the molecular basis of extravasation of cancer cells.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Mihoko Sutoh
authors.initials: MS
authors.lastname: Yoneyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.forename: Hisao
authors.initials: H
authors.lastname: Saitoh
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Yamaya
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Funyu
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D001749:Urinary Bladder Neoplasms / Q000473:pathology*