Institute of Immunology, Witten/Herdecke University, 58448 Witten, Germany.
Curr Mol Med. 2010 Jun;10(4):381-6. doi: 10.2174/156652410791317020.
Fast growing solid tumors generally lack an inner organisation, which causes the problem of a sufficient nutrient of each part of the tumor that then happens only by diffusion. The low oxygen supply leads to the activation of hypoxia-inducible factors, which regulate a plethora of genes. The reaction of tumor cells to hypoxia can be divided into two parts: On the one hand, there are signal substances, predominantly growth factors and cytokines, which provoke the vascularisation (angiogenesis), lymph vessel development (lymphangiogenesis), and the innervation (neoneurogenesis) of tumors and thus connect the tumor to structures of the environment. On the other hand, genes for intracellular proteins and receptors are regulated, which lead to changes of the tumor cell functions. Best characterized is the metabolic shift, a high anaerobic glycolytic activity and simultaneously a reduction of respiration. Furthermore, proliferation, dedifferentiation, resistance to apoptosis, and the metastatic potential are affected. With regard to the latter, we herein show that the migratory activity and velocity of PC-3 human prostate carcinoma cells significantly increases under oxygen-deprivation, which might be an explanation for the increasing number of experimental and clinical hints, that an anti-angiogenic therapy can promote the metastasis formation.
快速生长的实体瘤通常缺乏内部组织，这导致肿瘤的每个部位都不能得到足够的营养，只能通过扩散来获得营养。低氧供应会导致缺氧诱导因子的激活，这些因子调节着大量的基因。肿瘤细胞对缺氧的反应可以分为两部分：一方面，有信号物质，主要是生长因子和细胞因子，它们引发血管生成（血管生成）、淋巴管发育（淋巴管生成）和肿瘤的神经生成（神经生成），从而将肿瘤与环境结构连接起来。另一方面，调节细胞内蛋白质和受体的基因，导致肿瘤细胞功能发生变化。代谢转变的特征最为明显，即无氧糖酵解活性增加，同时呼吸减少。此外，增殖、去分化、抗凋亡和转移潜能也受到影响。关于后者，我们在此表明，在缺氧条件下，人前列腺癌细胞 PC-3 的迁移活性和速度显著增加，这可能解释了越来越多的实验和临床提示，即抗血管生成治疗可以促进转移的形成。
