Heat shock protein 70 (Hsp70) is frequently overexpressed in many different
tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of
tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal
tumor biomarker. Since viable, mHsp70-positive
tumor cells actively release Hsp70 in
lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal
tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of
circulating tumor cells (CTCs) in patients with different
tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of
tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and
EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using
cytokeratin and CD45-specific
antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic
breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during
therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different
tumors, an Hsp70 mAb-based selection system appears superior to an
EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive
biomarker for therapeutic failure in early-stage
tumors and as a target for the isolation of CTCs in various
tumor diseases.