Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
Adv Exp Med Biol. 2018;1092:91-112. doi: 10.1007/978-3-319-95294-9_6.
A defining hallmark of cancer and cancer development is upregulated angiogenesis. The vasculature formed in tumors is structurally abnormal, not organized in the conventional hierarchical arrangement, and more permeable than normal vasculature. These features contribute to leaky, tortuous, and dilated blood vessels, which act to create heterogeneous blood flow, compression of vessels, and elevated interstitial fluid pressure. As such, abnormalities in the tumor vasculature not only affect the delivery of nutrients and oxygen to the tumor, but also contribute to creating an abnormal tumor microenvironment that further promotes tumorigenesis. The role of chemical signaling events in mediating tumor angiogenesis has been well researched; however, the relative contribution of physical cues and mechanical regulation of tumor angiogenesis is less understood. Growing research indicates that the physical microenvironment plays a significant role in tumor progression and promoting abnormal tumor vasculature. Here, we review how mechanical cues found in the tumor microenvironment promote aberrant tumor angiogenesis. Specifically, we discuss the influence of matrix stiffness and mechanical stresses in tumor tissue on tumor vasculature, as well as the mechanosensory pathways utilized by endothelial cells to respond to the physical cues found in the tumor microenvironment. We also discuss the impact of the resulting aberrant tumor vasculature on tumor progression and therapeutic treatment.
癌症和癌症发展的一个显著特征是血管生成上调。肿瘤中形成的脉管系统结构异常，没有按照传统的层次排列进行组织，并且比正常脉管系统更具渗透性。这些特征导致血管渗漏、扭曲和扩张，从而导致血流不均匀、血管受压和间质液压力升高。因此，肿瘤脉管系统的异常不仅影响营养物质和氧气向肿瘤的输送，还导致形成异常的肿瘤微环境，进一步促进肿瘤发生。化学信号事件在介导肿瘤血管生成中的作用已经得到了很好的研究；然而，物理线索和机械调节对肿瘤血管生成的相对贡献还不太了解。越来越多的研究表明，物理微环境在肿瘤进展和促进异常肿瘤血管生成中起着重要作用。在这里，我们回顾了肿瘤微环境中的机械线索如何促进异常肿瘤血管生成。具体来说，我们讨论了肿瘤组织中基质硬度和机械应力对肿瘤血管生成的影响，以及内皮细胞利用的机械感觉途径来响应肿瘤微环境中发现的物理线索。我们还讨论了由此产生的异常肿瘤血管生成对肿瘤进展和治疗治疗的影响。
