Martin V, Liu D, Fueyo J, Gomez-Manzano C
Department of Neuro-Oncology, Brain Tumor Center, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Histol Histopathol. 2008 Jun;23(6):773-80. doi: 10.14670/HH-23.773.
The tyrosine kinase receptor Tie2 was initially identified as a specific vascular growth factor that governed several properties of endothelial cells under both physiological and pathological conditions. It was subsequently found that angiopoietins, the natural ligands of Tie2, modulate Tie2-dependent signaling, which in turn regulates the survival and apoptosis of endothelial cells, controls vascular permeability, and regulates the capillary sprouting that occurs during normal angiogenesis such as through development and ovarian remodeling. Tie2 also seems to play a crucial role in several vascular abnormalities, such as familial venous malformations. Beyond its critical role in angiogenesis, Tie2 also appears to maintain the long-term population and quiescent status of hematopoietic stem cells in the bone marrow stem cell niche. In cancer, Tie2 was originally found to be overexpressed in tumoral vessels. More recently, our laboratory and others have found that Tie2 is also expressed outside the vascular compartment in several types of cancer, including leukemia and solid neoplasms such as gastric tumors, breast tumors, and gliomas. The role of Tie2 in these tumoral cells is currently being explored. In this regard, our group reported the importance of Tie2-expressing glioma cells in their adhesion to the tumoral microenvironment. Because cancer may be considered as a complex organ with several cellular lineages coexisting in the same tumor, the expression of Tie2 by different tumoral compartments makes this cellular receptor an attractive target for cancer therapy.
酪氨酸激酶受体Tie2最初被鉴定为一种特定的血管生长因子，在生理和病理条件下均调控内皮细胞的多种特性。随后发现，Tie2的天然配体血管生成素可调节Tie2依赖性信号传导，进而调节内皮细胞的存活和凋亡，控制血管通透性，并调节正常血管生成过程中发生的毛细血管芽生，如在发育和卵巢重塑过程中。Tie2似乎在多种血管异常中也起着关键作用，如家族性静脉畸形。除了在血管生成中的关键作用外，Tie2似乎还维持骨髓干细胞龛中造血干细胞的长期数量和静止状态。在癌症中，最初发现Tie2在肿瘤血管中过度表达。最近，我们实验室和其他研究发现，Tie2也在几种癌症的血管外区域表达，包括白血病和实体瘤，如胃癌、乳腺癌和神经胶质瘤。目前正在探索Tie2在这些肿瘤细胞中的作用。在这方面，我们团队报道了表达Tie2的神经胶质瘤细胞在其与肿瘤微环境黏附中的重要性。由于癌症可被视为一个复杂的器官，同一肿瘤中存在多种细胞谱系，不同肿瘤区域对Tie2的表达使得这种细胞受体成为癌症治疗的一个有吸引力的靶点。
