Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

Int J Oncol. 2012 May;40(5):1455-69. doi: 10.3892/ijo.2012.1348. Epub 2012 Jan 27.


Lung cancer is commonly associated with multi-organ metastasis, and the bone is a frequent metastatic site for lung cancer. However, the molecular mechanism of organ-specific metastasis remains poorly understood. To elucidate this issue, we analyzed in this study genome-wide gene expression profiles of 15 metastatic lesions from three organs (bone, lung and liver) in a mouse model with multi-organ metastasis properties of human non-small cell lung cancer cells (ACC-LC319/bone2), using a combination of laser-microbeam microdissection and DNA microarrays. We identified 299 genes that could potentially be involved in the organ-selective nature of lung cancer metastasis. Among them, 77 were bone-specifically expressed elements, including genes involved in cell adhesion, cytoskeleton/cell motility, extracellular matrix remodeling and cell-cell signaling as well as genes already known to be involved in the bone metastasis of breast cancers. Quantitative RT-PCR confirmed the specific upregulation of eight genes in bone metastasis tumors, suggesting that these genes may be involved in bone metastasis. Our findings should be helpful for a better understanding of the molecular aspects of the metastatic process in different organs, and could lead to molecular target-based anticancer drugs and prevention of metastasis, especially bone metastasis.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Line, Tumor
  • Cluster Analysis
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Laser Capture Microdissection
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction