title: Hsp60 is actively secreted by human tumor cells.
abstract: 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.
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Merendino
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Claudia
authors.initials: C
authors.lastname: Campanella
authors.forename: Vito
authors.initials: V
authors.lastname: Marcianò
authors.forename: Anna
authors.initials: A
authors.lastname: Ribbene
authors.forename: Sabrina
authors.initials: S
authors.lastname: David
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
authors.forename: Giosalba
authors.initials: G
authors.lastname: Burgio
authors.forename: Davide F V
authors.initials: DF
authors.lastname: Corona
authors.forename: Everly
authors.initials: E
authors.lastname: Conway de Macario
authors.forename: Alberto J L
authors.initials: AJ
authors.lastname: Macario
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
mesh_terms: 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
chemical_list: D018834:Chaperonin 60; D017077:Culture Media, Conditioned; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C039465:5-dimethylamiloride; D000584:Amiloride; D000110:Acetylcholinesterase