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

Stephanie Breuninger, Stefan Stangl, Caroline Werner, Wolfgang Sievert, Dominik Lobinger, Gemma A. Foulds, Sarah Wagner, Anja Pickhard, Guido Piontek, Konrad Kokowski, Alan G. Pockley, Gabriele Multhoff

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish
Article number497
JournalFrontiers in Oncology
StatePublished - 2018
Externally publishedYes


  • Circulating tumor cells (CTCs)
  • CmHsp70.1 antibody
  • EpCAM (CD326)
  • Epithelial-to-mesenchymal transition (EMT)
  • Membrane Hsp70


Dive into the research topics of 'Membrane Hsp70-A novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition'. Together they form a unique fingerprint.

Cite this