Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.
Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.
复制标题
人类平滑肌细胞的基因表达程序：乳腺癌中组织特异性分化和预后意义。
DOI：
10.1371/journal.pgen.0030164
复制
发表时间：
2007-09
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
平滑肌存在于各种解剖学位置，如血管、各种内脏器官和毛囊。平滑肌的收缩对于诸如排尿、排尿、呼吸和维持血管张力等多种功能是重要的。尽管平滑肌细胞（SMCs）的生理作用各不相同，但我们对其功能和解剖学特化的异质性只有有限的了解。作为了解SMC从不同的解剖位置之间的内在差异的一步，我们使用DNA微阵列来配置文件的全球基因表达模式在36 SMC样品从不同的组织后，在细胞培养的规定条件下繁殖。从血管、支气管和内脏器官中分离的细胞之间存在显著差异。此外，内脏器官亚组中普遍存在差异，似乎反映了器官发生所必需的不同分子途径以及参与器官特异性收缩和生理特性的分子途径。最后，我们试图了解这种多样性如何有助于SMC参与病理学。我们发现，血管平滑肌细胞对血清暴露的反应的基因表达特征与人类癌症的预后显著较差相关，可能将血管损伤反应与肿瘤进展联系起来。据估计，人体含有大约200-400种不同的细胞类型。这些估计主要基于细胞的形态学特征，并且已经产生了平滑肌细胞的类别，其具有独特的外观并且存在于多种组织中。通过使用DNA微阵列来询问解剖学上不同的平滑肌细胞的基因表达，我们能够准确地梳理出许多经典分类为平滑肌细胞的不同细胞亚型。值得注意的是，这些新发现的不同亚型所表达的基因证实了它们的许多已知生物学特性，并提供了关于它们对特定疾病状态的易感性、保留的发育程序和潜在的药物靶点的线索。此外，从血管损伤的平滑肌细胞模型中，我们能够提取基因表达特征，为人类乳腺癌提供预后信息。对肿瘤进展建模特别感兴趣的是发现该基因表达特征与肿瘤缺氧相关。这项研究大大增加了我们对细胞多样性的理解，以及这种多样性对正常生理和疾病的贡献。
Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression. It has been estimated that the human body contains approximately 200–400 distinct cell types. These estimates are largely based on the morphological characteristics of cells and have yielded, among many others, the category of smooth muscle cells, which have a distinct appearance and are present in a wide variety of tissues. By using DNA microarrays to interrogate the gene expression of anatomically varying smooth muscle cells, we were able to accurately tease apart many of the distinct cell subtypes that are classically categorized as smooth muscle cells. Remarkably, genes expressed by these newly identified, distinct subtypes corroborate many of their known biological properties and give clues about their susceptibility to specific disease states, retained developmental programs, and potential drugable targets. Additionally, from a smooth muscle cell model of vascular injury, we were able to extract a gene expression signature that provides prognostic information for human breast cancers. Of particular interest for modeling tumor progression was the finding that this gene expression signature was associated with tumor hypoxia. This study adds much to our ever-growing depth of understanding of cellular diversity and the contributions of this diversity to normal physiology and disease.