Invadopodia in context.

Invadopodia in context.
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上下文中的Invadopodia。

DOI:
10.4161/cam.28349
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发表时间:
2014
影响因子:
3.2
通讯作者:
Gligorijevic B
Gligorijevic B
中科院分区:
生物学3区
文献类型:
--
作者:
Bergman A;Condeelis JS;Gligorijevic B

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侵袭足是可移动的肿瘤细胞中的动态突起,其功能是降解细胞外基质,使细胞能够进入新的环境。侵袭性突起在显微镜下被鉴定为含有TKS5和皮质动蛋白的蛋白水解性侵袭性突起。研究介体的模型越来越复杂,包括工程3D环境、外植体或体内动物模型,这就需要更高水平的微环境复杂性以及癌细胞的异质性。这样的实验设置蕴含着丰富的信息,并提供了将内向和其他与运动相关的结构联系起来的可能性。也就是说,它们有望揭示更现实的微环境条件,在这些微环境条件下,内含子组装和功能,或者肿瘤细胞转换到不同的细胞表型(局灶性粘连、片状脂膜、增殖和凋亡)。对于这样的努力,我们需要一种系统的显微镜方法,它将整合来自多种模式的信息。虽然实现这一目标所需的各种技术大多是可用的,但数据集成和标准化并不是一个微不足道的过程。在系统显微镜方法中,显微镜被用来提取关于细胞表型和微环境的信息,而组学技术则评估癌细胞和微环境的遗传、转录、翻译和蛋白质组成的特征。通过电子建模(包括统计和数学模型以及生物信息学)对数据进行分类和链接。计算方面的考虑创造了预测,通过使用遗传操作和分子生物学对系统进行扰动,从而在实验上验证预测。通过这种整体的方法,将达到对活体内跨足动物功能的更深层次的理解,从而为个性化诊断和治疗打开了可能性。
Invadopodia are dynamic protrusions in motile tumor cells whose function is to degrade extracellular matrix so that cells can enter into new environments. Invadopodia are specifically identified by microscopy as proteolytic invasive protrusions containing TKS5 and cortactin. The increasing complexity in models for the study of invadopodia, including engineered 3D environments, explants, or animal models in vivo, entails a higher level of microenvironment complexity as well as cancer cell heterogeneity. Such experimental setups are rich in information and offer the possibility of contextualizing invadopodia and other motility-related structures. That is, they hold the promise of revealing more realistic microenvironmental conditions under which the invadopodium assembles and functions or in which tumor cells switch to a different cellular phenotype (focal adhesion, lamellipodia, proliferation, and apoptosis). For such an effort, we need a systemic approach to microscopy, which will integrate information from multiple modalities. While the individual technologies needed to achieve this are mostly available, data integration and standardization is not a trivial process. In a systems microscopy approach, microscopy is used to extract information on cell phenotypes and the microenvironment while -omics technologies assess profiles of cancer cell and microenvironment genetic, transcription, translation, and protein makeups. Data are classified and linked via in silico modeling (including statistical and mathematical models and bioinformatics). Computational considerations create predictions to be validated experimentally by perturbing the system through use of genetic manipulations and molecular biology. With such a holistic approach, a deeper understanding of function of invadopodia in vivo will be reached, opening the potential for personalized diagnostics and therapies.
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