Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer.
Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer.
复制标题
DOI：
10.1186/1471-2407-9-244
复制
发表时间：
2009-07-20
期刊：
影响因子：
3.8
通讯作者：
Morin PJ
中科院分区：
文献类型：
--
作者：
Li J;Sherman-Baust CA;Tsai-Turton M;Bristow RE;Roden RB;Morin PJ
由于缺乏高度敏感和特异性的血清生物标志物，卵巢癌的大规模筛查是不可能的。claudin蛋白在卵巢癌中经常过度表达，但其作为预后、诊断或检测标志物的潜力尚不清楚。在这里，我们探索了这些蛋白作为卵巢癌检测筛选生物标志物的可能性。用条件培养基免疫印迹法检测细胞中Claudin蛋白的脱落情况。通过蔗糖梯度分离和免疫金电镜实验证实了卵巢癌细胞释放的外泌体中存在claudin。在63名卵巢癌患者和50名健康志愿者的试点小组中，评估了卵巢癌患者血浆中含有claudin -4的外泌体。在这些样本中还评估了CA125标记物，并与claudin-4阳性进行了比较。我们发现全长claudio可以从培养的卵巢癌细胞中脱落，并在培养基中作为称为外泌体的小脂质囊泡的一部分被发现。此外，来自卵巢癌患者的63份血浆样本中有32份显示含有claudin-4的外泌体的存在。相比之下，来自非癌症个体的50个样本中只有一个显示出claudin-4阳性外泌体。在我们的小样本中，特异性为98%，claudin-4和CA125检测的敏感性分别为51%和71%。这两个测试似乎不是独立的，而是密切相关的。我们的工作首次表明claudin-4可以从卵巢癌细胞中释放出来，并且可以在卵巢癌患者的外周循环中检测到。开发用于检测血液中claudin-4的灵敏试验对于确定该方法是否可以单独或与其他筛查方法联合用于检测卵巢癌至关重要。
The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection. Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity. We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated. Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.
登录
查看更多内容
影响因子：
4.7
作者：
Bignotti, Eliana;Tassi, Renata A.;Santin, Alessandro D.
通讯作者：
Santin, Alessandro D.
影响因子：
4.7
作者：
Hogdall, Estrid V. S.;Christensen, Lise;Hogdall, Claus K.
通讯作者：
Hogdall, Claus K.
影响因子：
45.3
作者：
Menon, U;Skates, SJ;Jacobs, IJ
通讯作者：
Jacobs, IJ
影响因子：
6
作者：
Hibbs, K;Skubitz, KM;Skubitz, APN
通讯作者：
Skubitz, APN
影响因子：
7.5
作者：
Lechpammer, Mirna;Resnick, Murray B.;Wang, Li J.
通讯作者：
Wang, Li J.