Dewing D, Emmett M, Pritchard Jones R
Department of Molecular and Clinical Cancer Medicine, Mersey Academic Plastic Surgery Group, Liverpool Cancer Research UK Centre, The Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
ISRN Oncol. 2012;2012:546927. doi: 10.5402/2012/546927. Epub 2012 Jun 7.
Blood vessels arose during evolution carrying oxygen and nutrients to distant organs via complex networks of blood vessels penetrating organs and tissues. Mammalian cells require oxygen and nutrients for survival, of which oxygen has a diffusion limit of 100 to 200 μm between cell and blood vessel. For growth beyond this margin, cells must recruit new blood vessels, first by vasculogenesis, where embryonic vessels form from endothelial precursors, then angiogenesis which is the sprouting of interstitial tissue columns into the lumen of preexisting blood vessels. Angiogenesis occurs in many inflammatory diseases and in many malignant disease states, including over 90% of solid tumours. Malignant melanoma (MM) is the most lethal skin cancer, highly angiogenic, highly metastatic, and refractory to all treatments. Raised serum levels of vascular endothelial growth factor (VEGF) strongly correlate MM disease progression and poor prognosis. Melanoma cells secrete several proangiogenic cytokines including VEGF-A, fibroblast growth factor (FGF-2), platelet growth factor (PGF-1), interleukin-8 (IL-8), and transforming growth factor (TGF-1) that modulate the angiogenic switch, changing expression levels during tumour transition from radial to invasive vertical and then metastatic growth. We highlight modern and historical lines of research and development that are driving this exciting area of research currently.
在进化过程中出现了血管，通过穿透器官和组织的复杂血管网络将氧气和营养物质输送到远处的器官。哺乳动物细胞需要氧气和营养物质来维持生存，其中氧气在细胞和血管之间的扩散极限为100至200μm。为了在这个范围之外生长，细胞必须首先通过血管生成来募集新的血管，即胚胎血管由内皮前体细胞形成，然后是血管生成，即间质组织柱向预先存在的血管腔内发芽。血管生成发生在许多炎症性疾病和许多恶性疾病状态中，包括超过90%的实体瘤。恶性黑色素瘤（MM）是最致命的皮肤癌，具有高度血管生成性、高度转移性，并且对所有治疗均具有抗性。血清血管内皮生长因子（VEGF）水平升高与MM疾病进展和不良预后密切相关。黑色素瘤细胞分泌几种促血管生成细胞因子，包括VEGF-A、成纤维细胞生长因子（FGF-2）、血小板生长因子（PGF-1）、白细胞介素-8（IL-8）和转化生长因子（TGF-1），这些细胞因子调节血管生成开关，在肿瘤从放射状生长转变为侵袭性垂直生长然后转移生长的过程中改变表达水平。我们重点介绍了目前推动这一令人兴奋的研究领域的现代和历史研究与开发路线。
