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The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences.

Publication ,  Journal Article
Graner, MW; Cumming, RI; Bigner, DD
Published in: J Neurosci
October 17, 2007

The heat shock response is a highly conserved "stress response" mechanism used by cells to protect themselves from potentially damaging insults. It often involves the upregulated expression of chaperone and heat shock proteins (HSPs) to prevent damage and aggregation at the proteome level. Like most cancers, brain tumor cells often overexpress chaperones/HSPs, probably because of the stressful atmosphere in which tumors reside, but also because of the benefits of HSP cytoprotection. However, the cellular dynamics and localization of HSPs in either stressed or unstressed conditions has not been studied extensively in brain tumor cells. We have examined the changes in HSP expression and in cell surface/extracellular localization of selected brain tumor cell lines under heat shock or normal environments. We herein report that brain tumor cell lines have considerable heat shock responses or already high constitutive HSP levels; that those cells express various HSPs, chaperones, and at least one cochaperone on their cell surfaces; and that HSPs may be released into the extracellular environment, possibly as exosome vesicular content. In studies with a murine astrocytoma cell line, heat shock dramatically reduces tumorigenicity, possibly by an immune mechanism. Additional evidence indicative of an HSP-driven immune response comes from immunization studies using tumor-derived chaperone protein vaccines, which lead to antigen-specific immune responses and reduced tumor burden in treated mice. The heat shock response and HSPs in brain tumor cells may represent an area of vulnerability in our attempts to treat these recalcitrant and deadly tumors.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

October 17, 2007

Volume

27

Issue

42

Start / End Page

11214 / 11227

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • Molecular Chaperones
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Heat-Shock Response
  • Heat-Shock Proteins
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor
  • Brain Neoplasms
 

Citation

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Graner, M. W., Cumming, R. I., & Bigner, D. D. (2007). The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences. J Neurosci, 27(42), 11214–11227. https://doi.org/10.1523/JNEUROSCI.3588-07.2007
Graner, Michael W., R Ian Cumming, and Darell D. Bigner. “The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences.J Neurosci 27, no. 42 (October 17, 2007): 11214–27. https://doi.org/10.1523/JNEUROSCI.3588-07.2007.
Graner, Michael W., et al. “The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences.J Neurosci, vol. 27, no. 42, Oct. 2007, pp. 11214–27. Pubmed, doi:10.1523/JNEUROSCI.3588-07.2007.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

October 17, 2007

Volume

27

Issue

42

Start / End Page

11214 / 11227

Location

United States

Related Subject Headings

  • Neurology & Neurosurgery
  • Molecular Chaperones
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Heat-Shock Response
  • Heat-Shock Proteins
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor
  • Brain Neoplasms