Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells

Sandeep Gurbuxani, Jean Marie Bruey, Annie Fromentin, Nicolas Larmonier, Arnaud Parcellier, Marja Jäättelä, François Martin, Eric Solary, Carmen Garrido

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 development of 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. When injected 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-free extracts 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 vivo. 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.

Original languageEnglish (US)
Pages (from-to)7478-7485
Number of pages8
JournalOncogene
Volume20
Issue number51
DOIs
StatePublished - Nov 8 2001
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Colonic Neoplasms
Neoplasms
Cell Death
Caspases
Nude Mice
Subcutaneous Injections
Cytochromes c
Cell Extracts
Transfection
Shock

Keywords

  • Apoptosis
  • Colon cancer cells
  • HSP70
  • Immunogenicity
  • Tumor-igenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Gurbuxani, S., Bruey, J. M., Fromentin, A., Larmonier, N., Parcellier, A., Jäättelä, M., ... Garrido, C. (2001). Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. Oncogene, 20(51), 7478-7485. https://doi.org/10.1038/sj.onc.1204948

Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. / Gurbuxani, Sandeep; Bruey, Jean Marie; Fromentin, Annie; Larmonier, Nicolas; Parcellier, Arnaud; Jäättelä, Marja; Martin, François; Solary, Eric; Garrido, Carmen.

In: Oncogene, Vol. 20, No. 51, 08.11.2001, p. 7478-7485.

Research output: Contribution to journalArticle

Gurbuxani, S, Bruey, JM, Fromentin, A, Larmonier, N, Parcellier, A, Jäättelä, M, Martin, F, Solary, E & Garrido, C 2001, 'Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells', Oncogene, vol. 20, no. 51, pp. 7478-7485. https://doi.org/10.1038/sj.onc.1204948
Gurbuxani S, Bruey JM, Fromentin A, Larmonier N, Parcellier A, Jäättelä M et al. Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. Oncogene. 2001 Nov 8;20(51):7478-7485. https://doi.org/10.1038/sj.onc.1204948
Gurbuxani, Sandeep ; Bruey, Jean Marie ; Fromentin, Annie ; Larmonier, Nicolas ; Parcellier, Arnaud ; Jäättelä, Marja ; Martin, François ; Solary, Eric ; Garrido, Carmen. / Selective depletion of inducible HSP70 enhances immunogenicity of rat colon cancer cells. In: Oncogene. 2001 ; Vol. 20, No. 51. pp. 7478-7485.
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