Abstract
BackgroundIn a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here.Principal FindingsWe found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevented by an inhibitor of this organelle.Conclusions/SignificanceWe propose a multistage process for the translocation of Hsp60 from the inside to the outside of the cell that includes a combination of protein traffic pathways and, ultimately, presence of the chaperonin in the circulating blood. The new information presented should help in designing future strategies for research and for developing diagnostic-monitoring means useful in clinical oncology.
Highlights
Molecular chaperones, many of which are Heat shock proteins (Hsps), are important players in protein homeostasis and cell and tissue physiology, as well as in protection against stressors [1]
Since Hsp60 was present in the plasma membrane fraction obtained from tumor cells, we performed experiments to determine if the chaperonin occurred in the lipid rafts fraction obtained from the same tumor cells
The data suggest that lipid rafts receive and internalize Hsp60 from the plasma membrane to intracellular vesicles, i.e., the microvesicular bodies (MVB), participating in Hsp60 trafficking at the plasma membrane level
Summary
Many of which are Heat shock proteins (Hsps), are important players in protein homeostasis and cell and tissue physiology, as well as in protection against stressors [1]. The importance of chaperones has come into focus in the last few years because it has been realized that they can be pathogenetic factors in a variety of conditions named chaperonopathies [1] Among these pathologies there are various forms of cancer (chaperonopathies ‘‘by mistake’’ or ‘‘by collaborationism’’), in which chaperones are normal but work in favor of the tumor rather than protect the patient [3]. In a previous work we showed for the first time that human tumor cells secrete Hsp via exosomes, which are considered immunologically active microvesicles involved in tumor progression This finding raised questions concerning the route followed by Hsp to reach the exosomes, its location in them, and whether Hsp can be secreted via other mechanisms, e.g., by the Golgi.
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