Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition

Breuninger, S, Stangl, S, Werner, C, Sievert, W, Lobinger, D, Foulds, GA ORCID: https://orcid.org/0000-0002-2053-7580, Wagner, S ORCID: https://orcid.org/0000-0002-5221-9851, Pickhard, A, Piontek, G, Kokowski, K, Pockley, AG ORCID: https://orcid.org/0000-0001-9593-6431 and Multhoff, G, 2018. Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition. Frontiers in Oncology, 8: 497. ISSN 2234-943X

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Abstract

The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)—an essential element of the metastatic process—is frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the “capture” of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)—cmHsp70.1—can be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression.

Item Type:	Journal article
Publication Title:	Frontiers in Oncology
Creators:	Breuninger, S., Stangl, S., Werner, C., Sievert, W., Lobinger, D., Foulds, G.A., Wagner, S., Pickhard, A., Piontek, G., Kokowski, K., Pockley, A.G. and Multhoff, G.
Publisher:	Frontiers Research Foundation
Date:	1 November 2018
Volume:	8
ISSN:	2234-943X
Identifiers:	Number Type 10.3389/fonc.2018.00497 DOI
Rights:	Copyright © 2018 Breuninger, Stangl, Werner, Sievert, Lobinger, Foulds, Wagner, Pickhard, Piontek, Kokowski, Pockley and Multhoff. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	09 Nov 2018 14:57
Last Modified:	01 Sep 2021 10:37
URI:	https://irep.ntu.ac.uk/id/eprint/34891

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