Oncotarget

Research Papers:

Exogenously delivered heat shock protein 70 displaces its endogenous analogue and sensitizes cancer cells to lymphocytes-mediated cytotoxicity

Maxim A. Shevtsov, Elena Y. Komarova, Darya A. Meshalkina, Natalia V. Bychkova, Nikolai D. Aksenov, Sergey V. Abkin, Boris A. Margulis and Irina V. Guzhova _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2014; 5:3101-3114. https://doi.org/10.18632/oncotarget.1820

Metrics: PDF 998 views  |   HTML 1413 views  |   ?  


Abstract

Maxim A. Shevtsov1,*, Elena Y.Komarova1,*, Darya A. Meshalkina1,*, Natalia V. Bychkova2, Nikolai D. Aksenov1, Sergey V. Abkin1, Boris A. Margulis1, Irina V. Guzhova1

1 Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russia

2 Laboratory of Clinical Immunology, EMERCOM of Russia, St.Petersburg, Russia

* These authors contributed equally to this work

Correspondence:

Irina V. Guzhova, email:

Keywords: heat shock protein 70, intra-, extracellular transport, cytotoxic lymphocytes, cancer cell.

Received: January 18, 2014 Accepted: March 20, 2014 Published: March 22, 2014

Abstract

Hsp70 chaperone is known to stimulate anti-tumour immunity in a variety of cancer models. Here we demonstrated that the addition of purified recombinant Hsp70 to the culture medium facilitated cancer cell cytolysis by lymphocytes. Importantly, exogenous Hsp70 triggered secretion of the intracellular Hsp70 to a cell surface and extracellular milieu, which played a role in cytolysis because down-regulation of the endogenous Hsp70 reduced both its presence at the cell surface and the lymphocyte-mediated cytolysis. Inhibitors that target both the ATPase and the peptide-binding domains of Hsp70 molecule potently decreased its anti-tumor effect. Using a variety of cell transport markers and inhibitors, we showed that the exchange of exogenous and intracellular Hsp70 is supported by classical and non-classical transport pathways, with a particular role of lipid rafts in the chaperone’s intracellular transport. In conclusion, exogenous Hsp70 can eject endogenous Hsp70, thus exerting anticancer activity.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 1820