INTERNALIZATION OF MICROBUBBLES BY TUMOR-CELLS IN-VIVO AND IN-VITRO
INTERNALIZATION OF MICROBUBBLES BY TUMOR-CELLS IN-VIVO AND IN-VITRO
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DOI：
10.1007/bf01054766
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发表时间：
1995-10-01
影响因子：
3.9
通讯作者：
SIMON, RH
中科院分区：
文献类型：
--
作者：
BARBARESE, E;HO, SY;SIMON, RH
静脉内（i. v.）给药的脂质包衣微泡（LCM）对荷瘤大鼠，特异性增强超声对肿瘤的显示[1]。为了理解这一观察的基础，我们已经研究了LCM与胶质母细胞瘤（C6）和胶质肉瘤（9 L）肿瘤细胞在体内和体外的相互作用。将LCM和用荧光亲脂性染料3，3 ′-双十八烷基氧碳菁高氯酸盐（diO）标记的LCM给药于荷瘤大鼠。LCM和diO标记的LCM主要在肿瘤部位发现，在周围正常脑组织中没有标记的证据。通过共聚焦激光扫描显微镜对肿瘤的分析显示，标记的LCM在肿瘤细胞内。对LCM与培养物中的C6和9 L细胞的相互作用的类似分析表明，LCM首先吸附在细胞的表面，并且随着时间的推移变得定位在细胞内。结合和内化在37 ° C下比在室温（RT）下进行得更快。用N-（3-（（2，4-二硝基苯基）氨基）丙基）-N-（3-氨基丙基）甲胺二盐酸盐（DAMP）（一种识别酸性区室的染料）对活细胞进行染色，表明大部分内化的LCM与含有DAMP的区室相关。如果相同的摄取机制在体内起作用，则表明LCM的一部分绕过网状内皮系统并直接被肿瘤细胞内吞。
Lipid-coated microbubbles (LCM) administered intravenously (i.v.) to rats bearing brain tumor, specifically enhance tumor visualization by ultrasound [1]. In order to understand the basis for this observation, we have examined the interactions of LCM with glioblastoma (C6) and gliosarcoma (9L) tumor cells in vivo and in vitro. LCM and LCM labeled with the fluorescent lipophilic dye 3,3'-dioctadecyloxacarbocyanine perchlorate (diO) were administered to rats bearing brain tumor. LCM and diO-labeled LCM were found principally at the tumor site with no evidence of label in the surrounding normal brain tissue. Analysis of the tumor by confocal laser scanning microscopy revealed that labeled LCM were inside the tumor cells. Similar analysis of LCM interactions with C6 and 9L cells in culture showed that LCM first adsorb at the surface of the cells, and with time became localized inside the cells. Binding and internalization proceeded faster at 37 degrees C than at room temperature (RT). Staining of live cells with N-(3-((2,4-dinitrophenyl)amino)propyl)-N-(3-aminopropyl) methylamine dihydrochloride (DAMP), a dye that recognizes acidic compartments, showed that the majority of internalized LCM was associated with compartments containing DAMP. If the same uptake mechanism were operative in vivo, it would indicate that a portion of LCM bypasses the reticuloendothelial system and become endocytosed directly by tumor cells.