Protein Interaction and Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
1] Tumour Angiogenesis Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
Oncogene. 2014 Jul 3;33(27):3496-505. doi: 10.1038/onc.2013.304. Epub 2013 Aug 5.
The growth and dissemination of tumors rely on an altered vascular network, which supports their survival and expansion and provides accessibility to the vasculature and a route of transport for metastasizing tumor cells. The remodeling of vascular structures through generation of new vessels (for example, via tumor angiogenesis) is a well studied, even if still quite poorly understood, process in human cancer. Antiangiogenic therapies have provided insight into the contribution of angiogenesis to the biology of human tumors, yet have also revealed the ease with which resistance to antiangiogenic drugs can develop, presumably involving alterations to vascular signaling mechanisms. Furthermore, cellular and/or molecular changes to pre-existing vessels could represent subtle pre-metastatic alterations to the vasculature, which are important for cancer progression. These changes, and associated molecular markers, may forecast the behavior of individual tumors and contribute to the early detection, diagnosis and prognosis of cancer. This review, which primarily focuses on the blood vasculature, explores current knowledge of how tumor vessels can be remodeled, and the cellular and molecular events responsible for this process.
肿瘤的生长和扩散依赖于改变的血管网络,该网络支持肿瘤的存活和扩张,并为肿瘤血管的可及性和转移肿瘤细胞的运输途径提供支持。通过生成新血管(例如,通过肿瘤血管生成)重塑血管结构是人类癌症中研究得很好但仍知之甚少的过程。抗血管生成疗法深入了解了血管生成对人类肿瘤生物学的贡献,但也揭示了对抗血管生成药物产生耐药性的容易程度,这可能涉及到血管信号机制的改变。此外,预先存在的血管的细胞和/或分子变化可能代表血管的细微转移前改变,这对癌症进展很重要。这些变化和相关的分子标志物可能预测肿瘤的行为,并有助于癌症的早期检测、诊断和预后。这篇综述主要关注血液血管系统,探讨了肿瘤血管如何重塑的现有知识,以及负责这一过程的细胞和分子事件。