Stec Małgorzata, Baj-Krzyworzeka Monika, Baran Jarosław, Węglarczyk Kazimierz, Zembala Maria, Barbasz Jakub, Szczepanik Antoni, Zembala Marek
Department of Clinical Immunology and Transplantation, Jagiellonian University Medical College, Cracow, Poland.
Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Cracow, Poland.
Oncol Rep. 2015 Nov;34(5):2768-75. doi: 10.3892/or.2015.4228. Epub 2015 Aug 26.
Micro(nano)vesicles (MV) are regarded as important messengers in cell-to-cell communication. There is also evidence for their pivotal role in cancer progression. Circulating MV are of different body cells origin, including tumor cell‑derived MV (TMV) in cancer patients. Determination of circulating TMV is of importance because of their potential diagnostic and therapeutic applications. In the present study, an analysis of circulating MV in colorectal cancer (CRC) patients was undertaken. Plasma from healthy donors was used as the control. In order to define MV characteristics, two plasma fractions: obtained by sequential centrifugation at 15,000 x g (MV15) and 50,000 x g (MV50) were used for analysis. The two fractions possessed a large range of sizes: 70(80)-1,300(1,400) nm and the most common particles with sizes 70-90 nm, both in patients and controls. Atomic force microscopy images of MV50 revealed a heterogeneous population of particles with different shapes and sizes. MV15 contained an increased level of CD41+ and CD61+ particles, suggesting their platelet origin. No difference between patients and controls was observed. A more precise analysis of MV50 showed the increased level of particles expressing EGFR (HER-1/Erb B1), HER-2/neu and Mucin1 (MUC1), suggesting their tumor origin. The total level of MV50‑expressing EGFR, HER-2/neu and MUC1 was enhanced in CRC patients. MV50 both of patients and controls attached to a colon cancer cell line (SW480) and to isolated blood monocytes at 2 h and were engulfed at 24 h. This uptake showed the lack of specificity. Thus, apart from the direct delivery of MV to the tumor site by plasma, monocytes carrying MV may also be involved in their transportation. Taken together, the presented data indicate that MV15 contain mainly platelet‑derived particles, while MV50 from CRC patients are enriched in TMV. Interaction of MV with cancer cells may pin-point their role in communication between tumor cells, resulting in molecular cargo exchange between them.
微（纳）泡（MV）被视为细胞间通讯的重要信使。也有证据表明它们在癌症进展中起关键作用。循环微泡源自不同的体细胞，包括癌症患者体内肿瘤细胞衍生的微泡（TMV）。由于其潜在的诊断和治疗应用价值，对循环TMV的测定具有重要意义。在本研究中，对结直肠癌（CRC）患者的循环微泡进行了分析。以健康供体的血浆作为对照。为了确定微泡的特征，使用通过在15,000×g（MV15）和50,000×g（MV50）下连续离心获得的两个血浆组分进行分析。在患者和对照中，这两个组分都具有广泛的尺寸范围：70（80）-1,300（1,400）nm，最常见的颗粒尺寸为70-90nm。MV50的原子力显微镜图像显示了具有不同形状和尺寸的颗粒异质群体。MV15含有水平升高的CD41 +和CD61 +颗粒，表明它们源自血小板。患者和对照之间未观察到差异。对MV50的更精确分析显示，表达表皮生长因子受体（EGFR，HER-1 / Erb B1）、HER-2 / neu和粘蛋白1（MUC1）的颗粒水平升高，表明它们源自肿瘤。CRC患者中表达EGFR、HER-2 / neu和MUC1的MV50的总水平升高。患者和对照的MV50在2小时时均附着于结肠癌细胞系（SW480）和分离的血液单核细胞，并在24小时时被吞噬。这种摄取缺乏特异性。因此，除了血浆将微泡直接递送至肿瘤部位外，携带微泡的单核细胞也可能参与其运输。综上所述，所呈现的数据表明MV15主要包含血小板衍生的颗粒，而CRC患者的MV50富含TMV。微泡与癌细胞的相互作用可能明确它们在肿瘤细胞间通讯中的作用，导致它们之间的分子货物交换。
