title: Establishment of a human lung cancer cell line with high metastatic             potential to multiple organs: gene expression associated with metastatic potential             in human lung cancer.
abstract: Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Nakano
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawashima
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kamiyoshihara
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kakegawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugano
authors.forename: Takashi
authors.initials: T
authors.lastname: Ibe
authors.forename: Toshiteru
authors.initials: T
authors.lastname: Nagashima
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Youichi
authors.initials: Y
authors.lastname: Ohtaki
authors.forename: Jun
authors.initials: J
authors.lastname: Atsumi
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D028861:Nuclear Pore Complex Proteins / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis / Q000235:genetics; D000081025:Sphingosine-1-Phosphate Receptors; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D000090802:rab7 GTP-Binding Proteins
chemical_list: C119724:AGFG1 protein, human; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins