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

肺腺癌细胞系高转移亚群的高转移能力机制及临床应用

• 批准号: 15590831
• 负责人: GEMMA Akihiko
• 金额: $ 2.24万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590831/
• 关键词: LUNG CANCER; METASTASIS; PROTEOME; cDNA array; Galectin-1; SiRNA; 2D-DIGE; CGH array

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.

为了鉴定肺癌中肿瘤转移的新的关键因素，我们在实验转移模型中建立了高转移性人肺腺癌细胞系，通过将细胞反复接种到裸鼠中，随后，培养从肺转移灶收集的肿瘤细胞，我们通过使用基因组-广泛的人cDNA微阵列分析，并将这些谱与亲本细胞系的谱进行比较。我们在高转移性细胞系中鉴定了新的基因，这些基因表现出显著增强或降低的表达。我们对肺癌细胞系亚群的分析表明，肺癌的高转移潜能可能不是由单个基因表达的改变引起的，而是由几个基因表达改变的积累引起的。在这项研究中，我们使用蛋白质组分析（2D-DIGE，Ab-array）和新开发的cDNA阵列，并确定了82个新的候选人，包括galectin-1。我们正在评估这些基因作为参与肺癌转移的关键分子;（1）通过实时RT-PCR、北方印迹和西方印迹证实这些表达，（2）通过SiRNA等证实这些功能，（3）应用免疫组化方法检测这些分子在临床标本中的应用价值。

项目成果

Yoshimura A: "Increased expression of the LGALS3 (galectin 3) gene in human non-small-cell lung cancer."Genes Chromosomes Cancer. 37(2). 159-164 (2003)

Yoshimura A：“人类非小细胞肺癌中 LGALS3（半乳糖凝集素 3）基因的表达增加。”基因染色体癌症。

The difference of angiogenesis in human lung adenocarcinoma cell lines with different metastatic potency

不同转移能力人肺腺癌细胞系血管生成的差异

• 发表时间: 2004
• 期刊: J Nippon Med Sch 71(3)
• 作者: 鈴木克洋;その他;Zou D
• 通讯作者: Zou D

Reduction of PTEN protein and loss of epidermal growth factor receptor(EGFR) gene mutation in lung cancer with natural resistance to gefitinib(IRESSA).

吉非替尼天然耐药肺癌（易瑞莎）中 PTEN 蛋白减少和表皮生长因子受体（EGFR）基因突变缺失。

• 期刊: Br J Cancer (in press)
• 作者: Yoshimura A;Kokubo Y;Okano T;Kokubo Y
• 通讯作者: Kokubo Y

The difference of angiogenesis in human lung adenocarcinoma cell lines with different metastatic potency.

不同转移能力的人肺腺癌细胞系血管生成的差异。

• 发表时间: 2004
• 期刊: J Nippon Med Sch. 71(3)
• 作者: Yoshimura A;Gemma A;Kataoka K;Hosoya Y;Noro R;Seike M;Kokubo Y;Watanabe M;Kudoh S.;鈴木克洋;Zou D
• 通讯作者: Zou D

Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer.

• DOI: 10.3892/or.15.3.545
• 发表时间: 2006-03
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: T. Okano;A. Gemma;Y. Hosoya;Y. Hosomi;M. Nara;Y. Kokubo;A. Yoshimura;M. Shibuya;M. Nagashima;C. Harris;S. Kudoh