Ran Sophia, Thorpe Philip E
Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8594, USA.
Int J Radiat Oncol Biol Phys. 2002 Dec 1;54(5):1479-84. doi: 10.1016/s0360-3016(02)03928-7.
(1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment.
Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125I-annexin V binding.
Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability.
Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy.
（1）确定磷脂酰丝氨酸（PS）是否在小鼠实体瘤的血管内皮上暴露。（2）确定肿瘤微环境中的条件是否能在组织培养中的存活内皮细胞上诱导PS暴露。
通过给小鼠注射抗PS单克隆抗体，并检查肿瘤和正常组织的冰冻切片中与血管内皮结合的抗PS抗体，来检测体内外化的PS。通过抗活性半胱天冬酶-3抗体或TUNEL检测来鉴定凋亡细胞。通过¹²⁵I-膜联蛋白V结合来确定培养的内皮细胞上的PS暴露情况。
抗PS抗体在六种肿瘤模型中特异性结合血管内皮。不同肿瘤类型中PS阳性血管的百分比在4%至40%之间。正常器官中的血管内皮未染色。很少有肿瘤血管表达凋亡标记物。缺氧/复氧、酸性、炎性细胞因子、凝血酶或过氧化氢可诱导培养的内皮细胞暴露PS，且不会导致细胞活力丧失。
肿瘤中的血管内皮细胞而非正常组织中的血管内皮细胞会外化PS。PS暴露可能由肿瘤相关的氧化应激和激活细胞因子诱导。PS是肿瘤血管丰富且易于检测的标记物，可用于肿瘤成像和治疗。
