Modeling of lung cancer by an orthotopically growing H460SM variant cell line reveals novel candidate genes for systemic metastasis

Jiang Liu, Fiona Blackball, Isolde Seiden-Long, Igor Jurisica, Roya Navab, Ni Liu, Nikolina Radulovich, Dennis Wigle, Muhajid Sultan, Jim Hu, Ming Sound Tsao, Michael R. Johnston

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6316-6324
Number of pages9
JournalOncogene
Volume23
Issue number37
DOIs
StatePublished - Aug 19 2004

Keywords

  • Expression profiling
  • Lung cancer
  • Metastatic model
  • Orthotopic model
  • Prognostic marker

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Liu, J., Blackball, F., Seiden-Long, I., Jurisica, I., Navab, R., Liu, N., Radulovich, N., Wigle, D., Sultan, M., Hu, J., Tsao, M. S., & Johnston, M. R. (2004). Modeling of lung cancer by an orthotopically growing H460SM variant cell line reveals novel candidate genes for systemic metastasis. Oncogene, 23(37), 6316-6324. https://doi.org/10.1038/sj.onc.1207795