Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer

BMC Cancer (Impact Factor: 3.36). 01/2009; 9.
Source: DOAJ




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.

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Available from: Richard B S Roden, Aug 14, 2014
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    • "TGFβ1 and MAGE3/6 are significantly more prevalent in malignant ovarian tumors than in benign lesions [35]. For screening biomarkers, claudin 4-positive exosomes were present in the plasma samples from 32 out of 63 ovarian cancer patients but only 1 out of 50 healthy individuals , raising the possibility that it could be used as a highly sensitive and specific indicator [48]. Other markers such as CD24 and EpCAM being expressed by ovarian carcinomas are exploited for the potential for diagnostics [49]. "
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    • "Early detection of cancer could be easily performed using exosomes isolated from body fluids such as blood plasma, serum, and urine. Evidence supporting this approach include: (1) ovarian cancer-associated expression of claudin proteins can be detected in the circulating vesicles of a majority of ovarian cancer patients [111], (2) in breast cancer patients increasing levels of circulating vesicles expressing CEA and the cancer antigen 15-3 is correlated with increasing size of tumors [105], (3) exosomes expressing tumor markers can be isolated from the sera of ovarian cancer patients and the amount increases along with tumor progression [29]; and (4) in glioblastoma patients, mRNA variants and microRNAs characteristic of gliomas could be detected in serum vesicles [28]. However, it was also found that not in all cases tumor-derived exosomes were present in the blood circulation [112]. "
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