Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery

Abstract

BACKGROUND Heat shock protein 60 (Hsp60) is a chaperonin involved in tumorigenesis, but its participation in tumor development and progression is not well understood and its value as a tumor biomarker has not been fully elucidated. In the current study, the authors presented evidence supporting the theory that Hsp60 has potential as a biomarker as well as a therapeutic target in patients with large bowel cancer. METHODS The authors studied a population of 97 subjects, including patients and controls. Immunomorphology, Western blot analysis, and quantitative real‐time polymerase chain reaction were performed on tissue specimens. Exosomes were isolated from blood and characterized by electron microscopy, biochemical tests, and Western blot analysis. RESULTS Hsp60 was found to be increased in cancerous tissue, in which it was localized in the tumor cell plasma membrane, and in the interstitium associated with cells of the immune system, in which it was associated with exosomes liberated by tumor cells and, as such, circulated in the blood. An interesting finding was that these parameters returned to normal shortly after tumor removal. CONCLUSIONS The data from the current study suggested that Hsp60 is a good candidate for theranostics applied to patients with large bowel carcinoma and encourage similar research among patients with other tumors in which Hsp60 has been implicated. Cancer 2015;121:3230–3239. © 2015 American Cancer Society.

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

“…Frequently, the immunopositivity for Hsp60, in cancerous tissue or circulating cancer cells, correlates with a poor prognosis [49,[51][52][53]. In contrast to these findings, we previously found that the loss of Hsp60 immunopositivity can be related to development and progression of bronchial cancer [54], which reflects the variety of roles that Hsp60 can play.…”

“…Various data support the hypothesis that Hsp60 favors carcinogenesis and show a close correlation between high levels of Hsp60 and different types of cancer, thus the immunopositivity for Hsp60 can be considered a biomarker useful for the diagnosis and monitoring these types of malignancies [33,[49][50]. Frequently, the immunopositivity for Hsp60, in cancerous tissue or circulating cancer cells, correlates with a poor prognosis [49,[51][52][53].…”

“…This could regulate the degradation of the chaperone by the ubiquitin-proteosome system [12,55]. Otherwise, the post-translational modifications could constitute a signal for extracellular secretion through the lipid raft pathway [11,49,56]. The function of extracellular Hsp60 is still under discussion.…”

Exosomes in cancer theranostic: Diamonds in the rough

“…Because of its presence in tumor cells but not in healthy cells, HSP60-exosomes seem to be also interesting biomarkers in cancer, at least for large bowel cancer diagnosis. 132 …”

Alzheimer's Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy

“…Hsp60 may influence tumor progression as suggested by its accumulation in the cytosol and plasma membrane of cancerous cells, reaching the extracellular space via secretory vesicles that in turn can modulate (induce, or inhibit?) anti-tumor immune responses [50][51][52]. Hyperacetylation of Hsp60 in osteosarcoma cells is associated with the anticancer activity of geldanamycin and Hsp60 nitration is associated with the anti-tumor action of the histone deacetylase inhibitor SAHA [53,54].…”