Angiogenic signaling aberrantly induced by tumor hypoxia.
Angiogenic signaling aberrantly induced by tumor hypoxia.
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DOI：
10.2741/3674
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
K. Takenaga
中科院分区：
文献类型：
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作者：
K. Takenaga
肿瘤的生长、侵袭和转移在很大程度上依赖于肿瘤血管的发育。大量的促血管生成和抗血管生成分子已被鉴定。骨髓来源的细胞通过多种生长因子和细胞因子被动员和募集到血管生成部位，以促进血管生成和新血管的形成。在实体瘤中不可避免地产生的缺氧微环境是肿瘤血管生成的主要贡献者。肿瘤缺氧异常地调节许多有效的促血管生成和抗血管生成分子的表达，主要通过称为缺氧诱导因子HIF-1和HIF-2的异二聚体转录因子的作用。促血管生成活性和抗血管生成活性之间的平衡的破坏最终导致平衡向更多血管生成状态的转变。这些发现引起了人们对HIF作为癌症治疗的有吸引力的靶点的极大兴趣。因此，小分子HIF抑制剂的开发目前正在快速推进。
Tumor growth, invasion and metastasis are largely dependent on the development of tumor vasculature. A great number of pro- and antiangiogenic molecules, have been identified. Bone marrow-derived cells are mobilized and recruited to angiogenic sites, by a variety of growth factors and cytokines, to promote angiogenesis and the formation of new blood vessels. The hypoxic microenvironment that is inevitably generated in solid tumors is a major contributor to tumor angiogenesis. Tumor hypoxia aberrantly modulates the expression of many potent pro- and antiangiogenic molecules, primarily through the action of heterodimeric transcription factors termed hypoxia-inducible factors, HIF-1 and HIF-2. The disruption of the balance between pro- and antiangiogenic activities eventually leads to a shift in balance to a more angiogenic state. These findings have provoked considerable interest in HIFs as attractive targets for cancer therapy. Consequently, the development of small molecule HIF inhibitors is currently moving ahead at a fast pace.