title: Modeling of lung cancer by an orthotopically growing H460SM variant cell line reveals novel candidate genes for systemic metastasis.
abstract: Endobronchial implantation of NCI-H460 cells into the nude rat generates a primary lung tumor with mediastinal lymph node spread, but rarely systemic metastases. We isolated tumor cells from mediastinal nodes, orthotopically reimplanted the cells into nude rats and repeated this four times to derive a cell line, designated H460SM, that spontaneously metastasizes to bone, kidney, brain, soft tissue and contralateral lung. H460SM cells demonstrated higher invasive activity in vitro than parental NCI-H460 cells. Spectral karyotyping revealed a new inversion within 17q and loss of an extra normal copy of chromosome 14 present in parental NCI-H460 cells. Expression profiling of orthotopic primary tumors revealed differential expression of 360 genes. Of these, 173 were represented in the probe set of a 19.2K OCI cDNA microarray previously used to profile the gene expression of surgically resected lung cancer specimens. We have computationally validated clinical importance of these genes by using in silico analysis of 18 cases of pulmonary adenocarcinoma, which were split into two patient groups with markedly different clinical outcome. The model identifies additional novel candidate genes for the progression of lung cancer to systemic metastases and poor prognosis.
authors.affiliation: Division of Thoracic Surgery, University Health Network, Princess Margaret Hospital and Ontario Cancer Institute, Ontario, Canada M5G 2M9.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
authors.forename: Isolde
authors.initials: I
authors.lastname: Seiden-Long
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Roya
authors.initials: R
authors.lastname: Navab
authors.forename: Ni
authors.initials: N
authors.lastname: Liu
authors.forename: Nikolina
authors.initials: N
authors.lastname: Radulovich
authors.forename: Dennis
authors.initials: D
authors.lastname: Wigle
authors.forename: Muhajid
authors.initials: M
authors.lastname: Sultan
authors.forename: Jim
authors.initials: J
authors.lastname: Hu
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Johnston
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018076:DNA, Complementary; D006801:Humans; D007621:Karyotyping; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
chemical_list: D018076:DNA, Complementary