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  Characterisation of tumour-derived microvesicles in cancer patients' blood and correlation with clinical outcome.

Menck, K., Bleckmann, A., Wachter, A., Hennies, B., Ries, L., Schulz, M., et al. (2017). Characterisation of tumour-derived microvesicles in cancer patients' blood and correlation with clinical outcome. Journal of Extracellular Vesicles, 6(1): 1340745. doi:10.1080/20013078.2017.1340745.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-B8C5-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-30F9-0
Genre: Journal Article

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 Creators:
Menck, K., Author
Bleckmann, A., Author
Wachter, A., Author
Hennies, B., Author
Ries, L., Author
Schulz, M., Author
Balkenhol, M., Author
Pukrop, T., Author
Schatlo, B., Author
Rost, U., Author
Wenzel, D.1, Author              
Klemm, F., Author
Binder, C., Author
Affiliations:
1Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578615              

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Free keywords: Cancer; extracellular vesicles; microvesicles; EMMPRIN; biomarker; tumour invasion
 Abstract: To evaluate whether tumour-derived microvesicles(T-MV), originating from the plasma membrane, represent suitable cancer biomarkers, we isolated MV from peripheral blood samples of cancer patients with locally advanced and/or metastatic solid tumours (n = 330, including 79 head & neck cancers, 74 lung cancers, 41 breast cancers, 28 colorectal cancers and 108 with other cancer forms) and controls (n = 103). Whole MV preparations were characterised using flow cytometry. While MV carrying the tumour-associated proteins MUC1, EGFR and EpCAM were found to be enhanced in a tumour-subtype-specific way in patients' blood, expression of the matrix metalloproteinase inducer EMMPRIN was increased independent of tumour type. Higher levels of EMMPRIN+-MV correlated significantly with poor overall survival, whereas the other markers were prognostic only in specific tumour subgroups. By combining all four tumour- associated antigens, cancer patients were separated from healthy controls with an AUC of up to 0.85. Ex vivo, whole MV preparations from cancer patients, in contrast to those of controls, induced a tumour-supporting phenotype in macrophages and increased tumour cell invasion, which was dependent on the highly glycosylated isoform of EMMPRIN. In conclusion, the detection of T-MV in whole blood, even in minor amounts, is feasible with standard techniques, proves functionally relevant and correlates with clinical outcome.

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Language(s): eng - English
 Dates: 2017-07-16
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1080/20013078.2017.1340745
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Title: Journal of Extracellular Vesicles
Source Genre: Journal
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Pages: 17 Volume / Issue: 6 (1) Sequence Number: 1340745 Start / End Page: - Identifier: -