Intracellular and extracellular Hsp70 chaperone as a target for cancer therapy

Abstract

The data presented in this paper show that endogenous Hsp70 protects cancer cells of different origins from a variety of cytotoxic threats including cancer cell therapeutics. In contrast, however, Hsp70 released from stressed cancer cells can serve as a danger signal or may recruit cells responsible for the generation of innate and adaptive immune responses against tumour cells.

Effects of Enzyme-Treated Asparagus Extract on Heat Shock Protein 70, Stress Indices, and Sleep in Healthy Adult Men

“…On the other hand, HSP70 released from the cell acts as a messenger to crosstalk with the immune system, and clinical hyperthermia could be a way to initiate the immunological activity of HSP70 (27). Recently, intracellular HSP70 has been reported to protect cancer cells from a variety of cytotoxic threats including chemotherapy, whereas extracellular HSP70 appears to help recruit cells responsible for the generation of innate and adaptive immune responses against tumor cells (28). Intracellular HSP70 consists of inducible HSP70 and constitutive HSP70, and both components may complement each other in a synergistic manner to preserve cellular integrity (29).…”

Hsp70 Induction and Anticancer Activity of U-133, the Acetylated Trisglucosydic Derivative of Echinochrome

“…On the other hand the appearance of Hsp70 at the surface of a cancer cell triggers activation of cytotoxic NK cells as proved by the group of Multhoff [19]. We can hypothesize that the NK cell-mediated destruction of tumor can lead to the appearance of Hsp70 complexes with tumor antigen, their incorporation to dendrytic cells, the event leading ultimately to the development of the specific anti-tumor activity represented by CD4 + and CD8 + cells [35,36]. Taken together, the experimental data suggest that Hsp70 induction serves to signal the immune system of the presence of an immunologically relevant (dangerous) situation against which an immune reaction should be raised [19,22,37,38].…”

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

“…To exploit the effects of hyperthermia on the immune system in the future, it will be especially important to fully understand the temperature dynamics and corresponding effects of the HSPs, since their role provokes the most tumour-specific immune response [90,91]. This is illustrated by the finding that Hsp70 can be used as an anti-cancer vaccine to mimic and maximise the response of hyperthermia [92,93].…”