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Titolo:
Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells
Autore:
Gurbuxani, S; Bruey, JM; Fromentin, A; Larmonier, N; Parcellier, A; Jaattela, M; Martin, F; Solary, E; Garrido, C;
Indirizzi:
Fac Med, INSERM, U517, IFR 100, F-21033 Dijon, France Fac Med Dijon France F-21033 NSERM, U517, IFR 100, F-21033 Dijon, France Danish Canc Soc, DK-2100 Copenhagen, Denmark Danish Canc Soc Copenhagen Denmark DK-2100 , DK-2100 Copenhagen, Denmark
Titolo Testata:
ONCOGENE
fascicolo: 51, volume: 20, anno: 2001,
pagine: 7478 - 7485
SICI:
0950-9232(20011108)20:51<7478:SDOIHE>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEAT-SHOCK-PROTEIN; HEAT-SHOCK-PROTEIN-70 INHIBITS APOPTOSIS; STRESS-INDUCED APOPTOSIS; CYTOCHROME-C; IMMUNE-RESPONSE; DIFFERENTIAL EXPRESSION; TUMOR IMMUNOGENICITY; ANTIGEN PRESENTATION; NEGATIVE REGULATION; APAF-1 APOPTOSOME;
Keywords:
HSP70; apoptosis; immunogenicity; tumorigenicity; colon cancer cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Garrido, C Fac Med, INSERM, U517, IFR 100, 7 Blvd Jeanne Darc, F-21033 Dijon, France Fac Med 7 Blvd Jeanne Darc Dijon France F-21033 Dijon, France
Citazione:
S. Gurbuxani et al., "Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells", ONCOGENE, 20(51), 2001, pp. 7478-7485

Abstract

Expression of inducible heat shock protein 70 (HSP70) in tumor cells has been proposed to enhance their immunogenicity. However, HSP70 has also been demonstrated to prevent tumor cell death, a key process for the developmentof tumor cell immunogenicity. In the present study, we investigated the influence of the HSP70 protein level on PRO colon cancer cell growth and immunogenicity in syngeneic BDIX rats and nude mice. These cells have a basal expression of HSP70 which can be substantially increased by heat shock. Wheninjected subcutaneously in syngeneic animals, PRO cells do not induce any detectable immune response and give rise to progressive, metastatic and lethal tumors. Stable transfection of an anti-sense hsp70 cDNA in PRO cells (PRO-70AS cells) strongly decreased HSP70 expression and sensitized cell-freeextracts to cytochrome c/dATP-mediated activation of caspases. Subcutaneous injection of PRO-70AS cells induced tumors that rapidly regressed in syngeneic rats while they grew normally in nude mice. Syngeneic rats injected with PRO-70AS cells became protected against a further challenge with PRO cells. The tumor-specific immune response induced by HSP70-depleted PRO-70AS cells was associated with an increased rate of cell death in viro. These PRO-70AS cells were also more sensitive to NO-mediated, caspase-dependent, macrophage cytotoxicity in vivo. Altogether, these results indicate that reduced level of HSP70 expression in PRO- colon cancer cells results in the generation of a specific immune response by promoting cell death in vivo.

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Documento generato il 23/09/20 alle ore 13:10:28