The mechanisms of highly metastetic capasity in highly metastatic subpopulations of lung adenocarcinoma cell line and these clinical applications

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To identify novel key factors of tumor metastasis in lung cancer, we established a highly metastatic human lung adenocarcinoma cell line in an experimental metastasis model by repeatedly inoculating the cells into nude mice and, subsequently, culturing tumor cells harvested from the pulmonary metastatic foci and we established the gene expression profiles of two adenocarcinoma cell line variants by use of genome-wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line. We identified novel genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression. Our analysis in subpopulations of a lung cancer cell line indicated that the highly metastatic potential of lung cancer may be induced not by an alteration in the expression of a single gene, but by the accumulation of alterations in the expression of several genes. In this study, we used proteome analysis (2D-DIGE, Ab-array) and newly-developed cDNA array and identified 82 novel candidates including galectin-1. We are evaluating these genes as key molecules involved in metastasis in lung cancer ; (1)confirm these expressions by real-time RT-PCR, Northern blot, and Western blot, (2)confirm these function by SiRNA et al., (3)evaluate clinical utility of these molecules by immunohistochemistry in clinical specimens.