TY - JOUR
T1 - Hsp60 is actively secreted by human tumor cells
AU - Cappello, Francesco
AU - Campanella, Claudia
AU - Corona, Davide
AU - Burgio, Giosalba
AU - Zummo, Giovanni
AU - Bucchieri, Fabio
AU - David, Sabrina
AU - Burgio, Giosalba
AU - De Macario, Everly Conway
AU - Corona, Davide F. V.
AU - Cappello, Francesco
AU - De Macario, Everly Conway
AU - Macario, Alberto J. L.
AU - Ribbene, Anna
AU - Merendino, Anna Maria
AU - Marciano', Vito
PY - 2010
Y1 - 2010
N2 - 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.METHODOLOGY/PRINCIPAL FINDINGS: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/SIGNIFICANCE: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.
AB - 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.METHODOLOGY/PRINCIPAL FINDINGS: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/SIGNIFICANCE: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.
UR - http://hdl.handle.net/10447/54468
M3 - Article
VL - 5(2)
JO - PLoS One
JF - PLoS One
SN - 1932-6203
ER -