Proteomic analysis of microvesicles derived from human colorectal cancer ascites

Proteomic analysis of microvesicles derived from human colorectal cancer ascites
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DOI:
10.1002/pmic.201100022
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发表时间:
2011-07-01
期刊:
影响因子:
3.4
通讯作者:
Gho, Yong Song
Gho, Yong Song
中科院分区:
生物学3区
文献类型:
--
作者:
Choi, Dong-Sic;Park, Jung Ok;Gho, Yong Song

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腹腔内恶性腹水的存在是生存率低的预后不良指标。各种癌细胞,包括结直肠癌(CRC)的那些,释放微泡(外来体)到周围组织和外周循环(包括恶性腹水)中。虽然最近的进展表明微泡在肿瘤进展中发挥多种作用,但恶性腹水来源的微泡的蛋白质组成和病理功能仍然未知。在这里,我们报告了第一个全球性的蛋白质组学分析高度纯化的微泡来自人CRC腹水。通过1-D SDS-PAGE和nano-LC-MS/MS分析,我们以高置信度从三名CRC患者的腹水中鉴定了总共846种微泡蛋白;在至少两名患者中鉴定了384种蛋白。我们鉴定了可能通过破坏上皮极性、迁移、侵袭、肿瘤生长、免疫调节和血管生成在肿瘤进展中起作用的蛋白质。此外,我们确定了几个潜在的CRC诊断标志物,包括结肠特异性表面抗原。我们的蛋白质组学分析将有助于阐明微泡在癌症进展中的各种功能,并有助于开发新的CRC诊断工具。
The presence of malignant ascites in the peritoneal cavity is a poor prognostic indicator of low survival rate. Various cancer cells, including those of colorectal cancer (CRC), release microvesicles (exosomes) into surrounding tissues and peripheral circulation including malignant ascites. Although recent progress has revealed that microvesicles play multiple roles in tumor progression, the protein composition and the pathological function of malignant ascites-derived microvesicles are still unknown. Here, we report the first global proteomic analyses of highly purified microvesicles derived from human CRC ascites. With 1-D SDS-PAGE and nano-LC-MS/MS analyses, we identified a total of 846 microvesicular proteins from ascites of three CRC patients with high confidence; 384 proteins were identified in at least two patients. We identified proteins that might function in tumor progression via disruption of epithelial polarity, migration, invasion, tumor growth, immune modulation, and angiogenesis. Furthermore, we identified several potential diagnostic markers of CRC including colon-specific surface antigens. Our proteomic analyses will help to elucidate diverse functions of microvesicles in cancer progression and will aid in the development of novel diagnostic tools for CRC.