Genome-wide analysis of organ-preferential metastasis of human small cell lung cancer in mice.
Although a number of molecules have been implicated in the process of cancer metastasis, the organ-selective nature of cancer cells is still poorly understood. To investigate this issue, we established a metastasis model in mice with multiple organ dissemination by i.v. injection of human small cell lung cancer (SBC-5) cells. We analyzed gene-expression profiles of 25 metastatic lesions from four organs (lung, liver, kidney, and bone) using a cDNA microarray representing 23,040 genes and extracted 435 genes that seemed to reflect the organ specificity of the metastatic cells and the cross-talk between cancer cells and microenvironment. Furthermore, we discovered 105 genes that might be involved in the incipient stage of secondary-tumor formation by comparing the gene-expression profiles of metastatic lesions classified according to size (<1 or >2 mm) as either "micrometastases" or "macrometastases." This genome-wide analysis should contribute to a greater understanding of molecular aspects of the metastatic process in different microenvironments, and provide indicators for new strategies to predict and prevent metastasis.
Kakiuchi
Soji
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Daigo
Yataro
Y
Tsunoda
Tatsuhiko
T
Yano
Seiji
S
Sone
Saburo
S
Nakamura
Yusuke
Y
D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology / Q000556:secondary; D007694:Killer Cells, Natural / Q000276:immunology; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008212:Lymphocyte Depletion; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured