title: Stress-induced release of HSC70 from human tumors.
abstract: In this study, we demonstrate that the pro-inflammatory cytokine interferon-gamma (IFN-gamma) induces the active release of the constitutive form of the 70-kDa heat shock protein (HSC70) from K562 erythroleukemic cells. Treatment of K562 cells with IFN-gamma induced the upregulation of the inducible form of the 70-kDa heat shock protein (HSP70), but not the constitutive form of HSC70 within the cytosol, in a proteasome-dependent manner. In addition, IFN-gamma induced the downregulation of surface-bound HSC70, but did not significantly alter surface-bound HSP70 expression. These findings indicate that HSC70 can be actively released from tumor cells and is indicative of a previously unknown mechanism by which immune modulators stimulate the release of intracellular HSC70. This mechanism may account for the potent chaperokine activity of heat shock proteins recently observed during heat shock protein-based immunotherapy against a variety of cancers.
authors.affiliation: Grupo de Inmunobiología and Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota, Colombia.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Barreto
authors.forename: John Mario
authors.initials: JM
authors.lastname: Gonzalez
authors.forename: Edith
authors.initials: E
authors.lastname: Kabingu
authors.forename: Alexzander
authors.initials: A
authors.lastname: Asea
authors.forename: Susana
authors.initials: S
authors.lastname: Fiorentino
mesh_terms: D003546:Cysteine Endopeptidases / Q000502:physiology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D020014:K562 Cells / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000502:physiology; D046988:Proteasome Endopeptidase Complex
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D007976:Leupeptins; D009097:Multienzyme Complexes; D016753:Interleukin-10; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde