Department of Chemistry, Brandeis University, Waltham, Massachusetts, United States of America.
PLoS One. 2016 Apr 21;11(4):e0154126. doi: 10.1371/journal.pone.0154126. eCollection 2016.
Identifying novel cancer biomarkers is important for early cancer detection as it can reduce mortality rates. The cancer secretome, the collection of all macromolecules secreted by a tumor cell, alters its composition compared to normal tissue, and this change plays an important role in the observation of cancer progression. The collection and accurate analysis of cancer secretomes could lead to the discovery of novel biomarkers, thus improving outcomes of cancer treatment. We unexpectedly discovered that enzyme-instructed self-assembly (EISA) of a D-peptide hydrogelator results in nanonets/hydrogel around cancer cells that overexpress ectophosphatases. Here we show that these nanonets are able to rapidly collect proteins in the pericellular space (i.e., near the surface) of cancer cells. Because the secretory substances are at their highest concentration near the cell surface, the use of pericellular nanonets to collect the cancer secretome maximizes the yield and quality of samples, reduces pre-analytical variations, and allows the dynamic profiling of secretome samples. Thus, this new approach has great potential in identifying the heterotypic signaling in tumor microenvironments thereby improving the understanding of tumor microenvironments and accelerating the discovery of potential biomarkers in cancer biology. Data are available via ProteomeXchange with identifier PXD003924.
鉴定新型癌症生物标志物对于早期癌症检测很重要，因为它可以降低死亡率。肿瘤细胞分泌的所有大分子组成的癌症分泌组与正常组织相比，其组成发生了改变，这种变化在观察癌症进展中起着重要作用。对癌症分泌组的收集和准确分析可能会发现新型生物标志物，从而改善癌症治疗的效果。我们意外地发现，D-肽凝胶因子的酶指导自组装（EISA）导致过表达外磷酸酶的癌细胞周围形成纳米网/水凝胶。在这里，我们表明这些纳米网能够快速收集癌细胞胞周空间（即靠近表面）中的蛋白质。由于分泌物质在细胞表面附近浓度最高，因此使用胞周纳米网收集癌症分泌组可以最大限度地提高样品的产量和质量，减少分析前的变化，并允许对分泌组样品进行动态分析。因此，这种新方法在鉴定肿瘤微环境中的异型信号方面具有很大的潜力，从而有助于加深对肿瘤微环境的理解，并加速癌症生物学中潜在生物标志物的发现。相关数据可在 ProteomeXchange 数据库中以标识符 PXD003924 查看。
