Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Wielicka Str. 265, 30-663, Cracow, Poland.
Cancer Immunol Immunother. 2010 Jun;59(6):841-50. doi: 10.1007/s00262-009-0808-2. Epub 2009 Dec 31.
Cell membrane microfragments called microvesicles (MV) originating from different cells are circulating in the blood of healthy subjects and their elevated numbers are found in different diseases, including cancer. This study was designed to characterise MV present in plasma of gastric cancer patients. Since majority of MV in blood are platelets-derived (PMV), plasma samples deprived of PMV were used. In comparison to control, the number of MV in patients was significantly elevated in all stages, higher in more advanced disease. Patients' MV showed an increased membrane expression of CCR6 and HER-2/neu. The proportion of MV carrying some leucocyte determinants was low and similar in patients and control. Transmission electron microscopy showed their substantial heterogeneity in size and shape. The size determined by dynamic light scattering analysis confirmed this heterogeneity. The MV size distribution in patients was broader within the range of 10-800 nm, while in control MV showed 3-mode distribution within the range of 10-400 nm. Atomic force microscopy confirmed MV size heterogeneity with implication that larger objects represented aggregates of smaller microparticles. Patients' MV exhibited increased absolute values of zeta potential, indicating a higher surface charge. Tumour markers HER-2/neu, MAGE-1, c-MET and EMMPRIN were detected both in control and patients' samples with stronger expression in the latter. Significantly higher expression of MAGE-1 and HER-2/neu mRNA was observed in individual patients. All together, it suggests that at least some MV in plasma of gastric cancer patients are tumour-derived. However, their role in cancer requires further studies.
细胞膜微碎片,称为微囊泡(MV),来源于不同的细胞,在健康受试者的血液中循环,其数量在包括癌症在内的不同疾病中升高。本研究旨在描述胃癌患者血浆中存在的 MV。由于血液中的大多数 MV 来源于血小板(PMV),因此使用去除了 PMV 的血浆样本。与对照组相比,所有阶段的患者 MV 数量均显著升高,在更晚期的疾病中更高。患者 MV 的 CCR6 和 HER-2/neu 膜表达增加。携带一些白细胞决定因素的 MV 比例较低,且在患者和对照组中相似。透射电子显微镜显示其在大小和形状上具有显著的异质性。动态光散射分析确定的 MV 大小证实了这种异质性。患者 MV 的大小分布在 10-800nm 范围内较宽,而对照组 MV 在 10-400nm 范围内呈 3 模式分布。原子力显微镜证实 MV 大小具有异质性,表明较大的物体代表较小的微颗粒的聚集体。患者 MV 的zeta 电位绝对值增加,表明表面电荷更高。HER-2/neu、MAGE-1、c-MET 和 EMMPRIN 等肿瘤标志物在对照组和患者样本中均有检测到,后者的表达更强。在个别患者中观察到 MAGE-1 和 HER-2/neu mRNA 的表达显著升高。综上所述,至少一些胃癌患者血浆中的 MV 是肿瘤来源的。然而,它们在癌症中的作用需要进一步研究。