Hsp60 is actively secreted by human tumor cells.
BACKGROUND
Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination.


RESULTS
Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts.


CONCLUSIONS
Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.
Merendino
Anna M
AM
Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.
Bucchieri
Fabio
F
Campanella
Claudia
C
Marcianò
Vito
V
Ribbene
Anna
A
David
Sabrina
S
Zummo
Giovanni
G
Burgio
Giosalba
G
Corona
Davide F V
DF
Conway de Macario
Everly
E
Macario
Alberto J L
AJ
Cappello
Francesco
F
D000110:Acetylcholinesterase / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D018834:Chaperonin 60 / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D047392:beta-Cyclodextrins / Q000494:pharmacology
D018834:Chaperonin 60; D017077:Culture Media, Conditioned; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C039465:5-dimethylamiloride; D000584:Amiloride; D000110:Acetylcholinesterase