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Angiogenesis, Metastasis, and the Cellular Microenvironment

Genome-Wide Analysis of Organ-Preferential Metastasis of Human Small Cell Lung Cancer in Mice¹

¹ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan;
² Laboratory for Medical Informatics, SNP Research Center, Riken (Institute of Physical and Chemical Research), Tokyo, Japan; and
³ Department of Internal Medicine and Molecular Therapeutics, The University of Tokushima School of Medicine, Tokushima, Japan

Requests for reprints: Yusuke Nakamura, 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. Phone: 81-3-5449-5372; Fax: 81-3-5449-5433. E-mail: yusuke{at}ims.u-tokyo.ac.jp

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.

Key Words: metastasis • microenvironment • small cell lung cancer • expression profile • therapeutic target

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