Identification of genes expressed in malignant cells that promote invasion.
Identification of genes expressed in malignant cells that promote invasion.
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DOI：
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发表时间：
2003-12
期刊：
影响因子：
11.2
通讯作者：
Jennifer Walter-Yohrling;Xiaohong Cao;Michele Callahan;W. Weber;S. Morgenbesser;S. Madden;Clarence J. Wang;B. Teicher
中科院分区：
文献类型：
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作者：
Jennifer Walter-Yohrling;Xiaohong Cao;Michele Callahan;W. Weber;S. Morgenbesser;S. Madden;Clarence J. Wang;B. Teicher
为了系统地鉴定与侵袭相关的基因，使用三维多细胞基质侵袭测定将人肿瘤细胞系分类为基质侵袭阳性或基质侵袭阴性。测定了来自基质隔室的两种主要细胞类型[内皮细胞（HMVEC）和肌成纤维细胞（HDF）]的细胞侵入肿瘤细胞簇（乳腺癌、卵巢癌、前列腺癌、肺癌和黑色素瘤）。四种肿瘤细胞系（MDA-MB 231、SKOV-3、A375和MEL 624）的侵袭评分为阳性，四种肿瘤细胞系（LNCaP、DU 145、PC 3和A549）的侵袭评分为阴性。通过GeneSpring层次聚类、t检验和卡方（2）检验分析从肿瘤细胞系产生的基因表达系列分析（SAGE）文库。出现反映细胞培养测定中的行为的簇。在47个差异表达最高的基因中，选择30个进行实时PCR确认，9个与基因表达标签计数的标准化系列分析具有良好的相关性。相关性最强的是骨髓基质抗原2、stathmin样蛋白3、肿瘤坏死因子受体超家族成员5和肝细胞生长因子酪氨酸激酶底物。转移性和非转移性卵巢癌的原位杂交显示，骨髓基质抗原2和肿瘤坏死因子受体超家族成员5在转移性疾病中的选择性表达。这种组合方法似乎是一个强大的工具，用于识别基因，可能是有用的诊断标志物和/或作为侵袭性实体瘤的治疗靶点。
To systematically identify genes related to invasion a three-dimensional multicellular matrix invasion assay was used to classify human tumor cell lines as stromal invasion positive or stromal invasion negative. Cells from two of the primary cell types of the stromal compartment [endothelial cells (HMVEC) and myofibroblasts (HDF)] were assayed for invasion into tumor cell clusters (breast carcinoma, ovarian carcinoma, prostate carcinoma, lung carcinoma, and melanoma). Four tumor cell lines (MDA-MB231, SKOV-3, A375, and MEL624) scored invasion positive, and four tumor cell lines (LNCaP, DU145, PC3, and A549) scored invasion negative. Serial analysis of gene expression (SAGE) libraries generated from the tumor cell lines were analyzed by GeneSpring Hierarchical clustering, t test, and chi(2) test. Clusters emerged that reflected the behavior in the cell culture assay. Of the 47 most highly differentially expressed genes, 30 were selected for confirmation by real-time PCR, and 9 had good correlation with normalized serial analysis of gene expression tag counts. The strongest correlations were for bone marrow stromal antigen 2, stathmin-like 3, tumor necrosis factor receptor superfamily member 5, and hepatocyte growth factor tyrosine kinase substrate. In situ hybridization of metastatic and nonmetastatic ovarian cancer demonstrated selective expression of bone marrow stromal antigen 2 and tumor necrosis factor receptor superfamily member 5 in the metastatic disease. This combination approach appears to be a powerful tool for identifying genes that may be useful as diagnostic markers and/or as therapeutic targets for invasive solid tumors.