Chaperonopathies and Chaperonotherapy. Hsp60 as Therapeutic Target in Cancer: Potential Benefits and Risks

Francesco      Cappello; Francesca      Angileri; Everly      Conway de Macario; Alberto      J. L. Macario

Abstract

In this minireview we focus on Hsp60 as a target for anticancer therapy. We discuss the new concepts of chaperonopathies and chaperonotherapy and present information on Hsp60 localization in the cell membrane of human tumor cells. We describe novel mechanisms for Hsp60 reaching the extracellular environment that involve membrane-associated stages, as well as data on anti-Hsp60 antibodies found in human sera, both in normal subjects and patients affected by autoimmune diseases. Finally, we discuss possible therapeutic applications of anti-Hsp60 antibodies in cancer treatment, evaluating also side effects on non-tumor cells. In conclusion, the way for investigating Hsp60-targeted anti-tumor therapy is open, at least for those tumors that express Hsp60 on its surface and/or secrete it outside the cell, as is the search for the molecular mechanisms involved in Hsp60 translocation from cytosol to cell membrane: elucidation of this mechanism will greatly facilitate the optimization of chaperonotherapy centered on Hsp60 with anti-tumor efficacy and minimal side effects.

Keywords: Hsp60, Cpn60, HSPD1, plasma membrane, antibodies, autoantibodies, antitumor immunotherapy, anticancer therapy, chaperonopathies, human sera.