Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

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

Jianghong Li1, Cheryl A Sherman-Baust1, Miyun Tsai-Turton2, Robert E Bristow34, Richard B Roden234 and Patrice J Morin12*

Author Affiliations

1 Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD, USA

2 Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

3 Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

4 Department of Gynecology & Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

For all author emails, please log on.

BMC Cancer 2009, 9:244  doi:10.1186/1471-2407-9-244

Published: 20 July 2009

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.