Tissue proteomics reveals differential and compartment-specific expression of the homologs transgelin and transgelin-2 in lung adenocarcinoma and its stroma.
Tissue proteomics reveals differential and compartment-specific expression of the homologs transgelin and transgelin-2 in lung adenocarcinoma and its stroma.
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DOI：
10.1021/pr900705r
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发表时间：
2009-12
影响因子：
4.4
通讯作者：
Wang, Julia Y.
中科院分区：
文献类型：
--
作者：
Rho, Jung-hyun;Roehrl, Michael H. A.;Wang, Julia Y.
发现人类癌症的组织特异性生物标志物对于癌症的早期诊断和分子理解至关重要。为了克服组织生物大分子动态浓度范围大和组成复杂的局限性，我们采用肝素亲和分离技术进行蛋白质组学富集。对5对正常肺组织和肺腺癌组织的蛋白质组进行二维差异凝胶电泳比较，发现有14个点存在差异表达。从这些候选点中，通过质谱分析鉴定了三种在癌症中过表达的蛋白，分别是transgelin (TAGLN, SM22-α, WS3-10), transgelin-2 （TAGLN2）和cyclophilin A （PPIA）。定量RT-PCR结果显示，TAGLN2和PPIA在转录水平均上调。使用独立的10对肺腺癌样本，通过Western blot分析验证差异蛋白表达水平。通过对人体组织切片的免疫组化，我们发现TAGLN的过表达严格局限于肿瘤诱导的反应性肌成纤维基质组织腔室，而TAGLN2的过表达则完全局限于肿瘤腺腔室。因此，高度同源的蛋白对TAGLN和TAGLN2在肿瘤基质细胞和肿瘤上皮细胞中表现出互斥的、室特异性的细胞类型表达调控。我们的数据进一步表明，TGLN可能是侵袭性癌附近活跃的间质重塑的标志。它可能揭示肿瘤-基质相互作用的机制，并可能有助于早期诊断，治疗指导和治疗反应监测。
Discovery of tissue-specific biomarkers for human cancer is crucial for early diagnosis and molecular understanding of the disease. To overcome the limitations posed by the large dynamic concentration range and compositional complexity of tissue biomacromolecules, we applied heparin affinity fractionation for proteomic enrichment. Comparing the proteomes of five paired samples of normal lung and pulmonary adenocarcinoma tissue by 2-D difference gel electrophoresis, 14 spots were found to be differentially expressed. From these candidate spots, three proteins overexpressed in cancer were identified by mass spectrometry as transgelin (TAGLN, SM22-α, WS3-10), transgelin-2 (TAGLN2), and cyclophilin A (PPIA). Quantitative RT-PCR indicated that both TAGLN2 and PPIA were upregulated at transcriptional level. Differential protein expression levels were validated by Western blot analysis using an independent set of 10 paired lung adenocarcinoma samples. Using immunohistochemistry on human tissue sections, we discovered that overexpression of TAGLN was strictly localized to the tumor-induced reactive myofibroblastic stromal tissue compartment, whereas overexpression of TAGLN2 was exclusively localized to the neoplastic glandular compartment. Thus, the highly homologous protein pair TAGLN and TAGLN2 displayed mutually exclusive, compartment-specific cell type expression regulation in tumor stroma vs. neoplastic epithelial cells. Our data further suggest that TGLN may be a marker of active stromal remodeling in the vicinity of invasive carcinomas. It may shed light on mechanisms of tumor-stroma interaction and could be useful for early diagnosis, treatment guidance, and treatment response monitoring.
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影响因子：
3.3
作者：
Fu, YP;Liu, HW;Solway, J
通讯作者：
Solway, J
影响因子：
9.6
作者：
Detterbeck, Frank C.;Boffa, Daniel J.;Tanoue, Lynn T.
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Tanoue, Lynn T.
DOI：
10.1016/j.biocel.2008.02.011
发表时间：
2009-03-01
影响因子：
4
作者：
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Prasad, Priya D.
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作者：
Grigoriev, VG;Thweatt, R;Goldstein, S
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影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.