TY - JOUR
T1 - Membrane Hsp70-A novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition
AU - Breuninger, Stephanie
AU - Stangl, Stefan
AU - Werner, Caroline
AU - Sievert, Wolfgang
AU - Lobinger, Dominik
AU - Foulds, Gemma A.
AU - Wagner, Sarah
AU - Pickhard, Anja
AU - Piontek, Guido
AU - Kokowski, Konrad
AU - Pockley, Alan G.
AU - Multhoff, Gabriele
N1 - Publisher Copyright:
© 2018 Frontiers Media S.A.All Rights Reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Circulating tumor cells (CTCs)
KW - CmHsp70.1 antibody
KW - EpCAM (CD326)
KW - Epithelial-to-mesenchymal transition (EMT)
KW - Membrane Hsp70
UR - http://www.scopus.com/inward/record.url?scp=85062615611&partnerID=8YFLogxK
U2 - 10.3389/fonc.2018.00497
DO - 10.3389/fonc.2018.00497
M3 - Article
AN - SCOPUS:85062615611
SN - 2234-943X
VL - 8
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 497
ER -