8 research outputs found
Morphological, molecular and cross-breeding analysis of geographic populations of coconut-mite associated predatory mites identified as Neoseiulus baraki: evidence for cryptic species?
Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia
Morphological variation and reproductive incompatibility of three coconut-mite-associated populations of predatory mites identified as Neoseiulus paspalivorus (Acari: Phytoseiidae)
Caspase-dependent, geldanamycin-enhanced cleavage of co-chaperone p23 in leukemic apoptosis
Spheroid growth in ovarian cancer alters transcriptome responses for stress pathways and epigenetic responses
Chaperonin Hsp60 and Cancer Therapies
The heat shock protein 60 (Hsp60) is a chaperonin belonging to the
chaperoning (chaperone) system that typically contributes to protein homeostasis
inside mitochondria, but also plays various non-canonical roles unrelated to protein
quality control beyond the organelle. Chaperonopathies are disorders in which
chaperones play an etiologic-pathogenic role and contribute to the onset/progression
of disease. Hsp60 chaperonopathies by mistake are diseases in which the chaperonin
is apparently normal (as far as it can be determined with current methodologies) but
it actively contributes to pathology, for example in certain types of cancer, and
autoimmune and chronic inflammatory disorders. In certain cancers, Hsp60 is
associated with the onset of malignancy and metastasization, although the mechanisms are poorly understood. In this chapter, we summarize findings on Hsp60
quantitative changes and distribution alterations in cells and tissues accompanying tumor initiation and progression. We also discuss the potential of HSP60-based anticancer therapies that are currently being investigated.Methods Journals and data bases were surveyed, and pertinent works were chosen
for discussion.
Results The data have stimulated experimental and clinical studies aiming at
establishing the usefulness of Hsp60 as biomarker for diagnosis, and for assessing
prognosis and response to treatment. Likewise, investigations are ongoing on the
possible use of Hsp60 as a therapeutic agent or target. The reported results indicate
that in neoplasms, Hsp60 migrates outside its canonical location, the mitochondrion,
augments in the cytoplasm and plasma-cell membrane, and exits the cell via lipid
rafts-exosomes. Exosomal Hsp60 occurs in extracellular fluids such as blood,
through which it reaches target cells near and far, normal or cancerous. With these
target cells, exosomes carrying Hsp60 and other molecules interact and, thereby,
modify their functions. Thus, detection of exosomal Hsp60 in body fluids appears as
a promising variety of liquid biopsy applicable to monitoring cancers already
diagnosed and to screen for malignancies before they are clinically manifest. We
also discuss Hsp60-based vaccines as a novel means of eliminating cancer cells with
cytotoxic T lymphocytes (CTL). Tumor-derived Hsp60 associated with a tumorderived antigen activates CD8+ T cells and induces an antitumor immune response.
It is highly probable that soon there will be implementation of clinical trials,
involving the use of Hsp60 alone or in various combinations and complexes to
prevent cancer progression and treat patients.
Conclusions Hsp60 is actively involved in tumor development and progression. Its
presence in extracellular fluids renders it a potential non-invasive biomarker. Also,
considering the antitumor activities of Hsp60 observed in some types of cancer one
can foresee a bright future for Hsp60-based therapies