Huang Ming-Bo, Xia Meng, Gao Zhao, Zhou Hu, Liu Min, Huang Shan, Zhen Rong, Wu Jennifer Y, Roth William W, Bond Vincent C, Xiao Jian, Leng Jing
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia, USA.
Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
J Cancer Ther. 2019 May;10(5):382-399. doi: 10.4236/jct.2019.105032. Epub 2019 May 29.
Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic bio-marker and as a possible therapeutic target.
由于循环肿瘤特异性DNA、RNA或蛋白质相对稀少,其检测可能会很困难。外泌体是细胞外囊泡,直径为30 - 150纳米,由多泡体与质膜融合产生。它们由脂质双分子层膜组成,包含蛋白质、mRNA和miRNA。外泌体由多种细胞类型分泌,包括癌细胞。然而,关于各种肿瘤细胞类型分泌的外泌体内容物的信息相对较少。为了研究癌症中的外泌体,我们收集了乳腺癌、卵巢癌、前列腺癌、肝癌、胃癌、结肠癌和胰腺癌患者的血浆样本。从血浆中分离出外泌体,并通过乙酰胆碱酯酶测定、透射电子显微镜和CD63外泌体标志物的表达进行确认。使用自动电化学发光测定法测定AFP、CA724、CA153、CEA、CA125、CA199和PSA抗原的表达。通过蛋白质印迹分析确定肿瘤相关伴侣蛋白mortalin的表达。不同肿瘤类型的外泌体分泌水平各不相同。除胰腺癌外,肿瘤细胞外泌体内的外泌体水平和mortalin表达均高于健康供体,在胰腺癌中,外泌体水平升高,但mortalin表达与健康供体无显著差异。外泌体为富集肿瘤特异性物质提供了独特的机会,可能作为生物标志物有用,也可能作为癌症治疗工具。Mortalin与细胞增殖和癌细胞上皮-间质转化的诱导有关,可能作为预后生物标志物和可能的治疗靶点有用。