Williams Steven P, Karnezis Tara, Achen Marc G, Stacker Steven A
Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
J Angiogenes Res. 2010 Aug 11;2:13. doi: 10.1186/2040-2384-2-13.
The lymphatic vascular system is actively involved in tissue fluid homeostasis, immune surveillance and fatty acid transport. Pathological conditions can arise from injury to the lymphatics, or they can be recruited in the context of cancer to facilitate metastasis. Protein tyrosine kinases are central players in signal transduction networks and regulation of cell behavior. In the lymphatic endothelium, tyrosine kinases are involved in processes such as the maintenance of existing lymphatic vessels, growth and maturation of new vessels and modulation of their identity and function. As such, they are attractive targets for both existing inhibitors and the development of new inhibitors which affect lymphangiogenesis in pathological states such as cancer. RNAi screening provides an opportunity to identify the functional role of tyrosine kinases in the lymphatics. This review will discuss the role of tyrosine kinases in lymphatic biology and the potential use of inhibitors for anti-lymphangiogenic therapy.
淋巴血管系统积极参与组织液稳态、免疫监视和脂肪酸运输。病理状况可能源于淋巴管损伤，或者在癌症背景下被募集以促进转移。蛋白质酪氨酸激酶是信号转导网络和细胞行为调节的核心参与者。在淋巴管内皮中，酪氨酸激酶参与诸如维持现有淋巴管、新血管的生长和成熟以及调节其特性和功能等过程。因此，它们是现有抑制剂以及开发影响癌症等病理状态下淋巴管生成的新抑制剂的有吸引力的靶点。RNA干扰筛选为确定酪氨酸激酶在淋巴管中的功能作用提供了机会。本综述将讨论酪氨酸激酶在淋巴生物学中的作用以及抑制剂在抗淋巴管生成治疗中的潜在用途。
