A peptide selected by biopanning identifies the integrin αvβ6 as a prognostic biomarker for nonsmall cell lung cancer
A peptide selected by biopanning identifies the integrin αvβ6 as a prognostic biomarker for nonsmall cell lung cancer
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DOI：
10.1158/0008-5472.can-07-0245
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发表时间：
2007-06-15
期刊：
影响因子：
11.2
通讯作者：
Brown, Kathlynn C.
中科院分区：
文献类型：
--
作者：
Elayadi, Anissa N.;Samli, Kausar N.;Brown, Kathlynn C.
肺癌诊断和靶向治疗新模式的发展依赖于对癌细胞独特细胞表面特征的识别，以及对这些生物标志物具有高亲和力和特异性的试剂的分离。我们最近从噬菌体展示肽库中分离出一种与肺腺癌细胞系H2009结合的20-mer肽。我们在这里表明，这种肽的细胞受体TP H2009.1是唯一表达的整合素α (v) β(6)，并且与肺癌细胞系结合的肽与整合素的表达相关。该肽能够通过该受体介导荧光纳米颗粒的细胞特异性摄取。在311例人类肺癌样本中评估了α (v) β(6)的表达。这种整合素在早期非小细胞肺癌（NSCLC）中广泛表达。Log-rank检验和Cox回归分析显示，该整合素的表达与患者预后不良显著相关。与周围正常肺组织相比，在肿瘤中观察到优先表达。我们的数据表明006是NSCLC的预后生物标志物，可能作为靶向治疗的受体。因此，从噬菌体生物计划中分离的细胞特异性肽可用于发现细胞表面生物标志物，强调肽库探测细胞表面的效用。
The development of new modes of diagnosis and targeted therapy for lung cancer is dependent on the identification of unique cell surface features on cancer cells and isolation of reagents that bind with high affinity and specificity to these biomarkers. We recently isolated a 20-mer peptide which binds to the lung adenocarcinoma cell line, H2009, from a phage-displayed peptide library. We show here that the cellular receptor for this peptide, TP H2009.1, is the uniquely expressed integrin, alpha(v)beta(6), and the peptide binding to lung cancer cell lines correlates to integrin expression. The peptide is able to mediate cell-specific uptake of a fluorescent nanoparticle via this receptor. Expression of alpha(v)beta(6) was assessed on 311 human lung cancer samples. The expression of this integrin is widespread in early-stage nonsmall cell lung carcinoma (NSCLC). Log-rank test and Cox regression analyses show that expression of this integrin is significantly associated with poor patient outcome. Preferential expression is observed in the tumors compared with the surrounding normal lung tissue. Our data indicate that 006 is a prognostic biomarker for NSCLC and may serve as a receptor for targeted therapies. Thus, cell-specific peptides isolated from phage biopanning can be used for the discovery of cell surface biomarkers, emphasizing the utility of peptide libraries to probe the surface of a cell.