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Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces.

Publication ,  Journal Article
Graner, MW; Raynes, DA; Bigner, DD; Guerriero, V
Published in: Cancer Sci
October 2009

Chaperone proteins and heat shock proteins (HSP) are essential components of cellular protein folding systems under normal conditions; their expression and activities are upregulated during stress. Chronically stressed tumors frequently exhibit high chaperone protein levels, exploiting their anti-apoptotic mechanisms and general proteome homeostasis amidst a background of genetic instability. Co-chaperones interact with chaperones as malleable regulatory components of protein folding activity and may represent a conduit for modification of chaperone activity to the detriment of the tumor. We have initially characterized one such co-chaperone, heat shock protein 70-binding protein (HspBP) 1 from human brain tumors, their xenografts grown in immune-compromised mice, and in syngeneic murine models in immune-competent mice. Immunohistochemical analyses show HspBP1 overexpression (with unusual subcellular localizations) in patient brain tumors relative to normal brain tissue. This holds true for the xenograft and syngeneic murine tumor models. In biochemical affinity chromatography assays, HspBP1 interacts with members of the HSP70 family from brain tumor lysates and from surface-derived samples, including HSP70, glucose regulated protein (GRP)75, GRP78, and HSP110. From normal brain lysates, only heat shock cognate (HSC)70, GRP75, and HSP110 bind to HspBP1. FACS analyses indicate that HspBP1 binds to brain tumor cell surfaces, possibly via HSP70 family members, and internalizes into cells. This has implications for HspBP1 biology as well as its utility as a tumor-targeting agent. Our results suggest that HspBP1 may play a role in tumor (dys)regulation of chaperone proteins, and that HspBP1 may have extracellular roles with therapeutic implications.

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Published In

Cancer Sci

DOI

EISSN

1349-7006

Publication Date

October 2009

Volume

100

Issue

10

Start / End Page

1870 / 1879

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tissue Array Analysis
  • Oncology & Carcinogenesis
  • Mice
  • Immunohistochemistry
  • Humans
  • HSP70 Heat-Shock Proteins
  • Glioma
  • Flow Cytometry
  • Endoplasmic Reticulum Chaperone BiP
 

Citation

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Graner, M. W., Raynes, D. A., Bigner, D. D., & Guerriero, V. (2009). Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces. Cancer Sci, 100(10), 1870–1879. https://doi.org/10.1111/j.1349-7006.2009.01269.x
Graner, Michael W., Deborah A. Raynes, Darell D. Bigner, and Vince Guerriero. “Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces.Cancer Sci 100, no. 10 (October 2009): 1870–79. https://doi.org/10.1111/j.1349-7006.2009.01269.x.
Graner, Michael W., et al. “Heat shock protein 70-binding protein 1 is highly expressed in high-grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces.Cancer Sci, vol. 100, no. 10, Oct. 2009, pp. 1870–79. Pubmed, doi:10.1111/j.1349-7006.2009.01269.x.
Journal cover image

Published In

Cancer Sci

DOI

EISSN

1349-7006

Publication Date

October 2009

Volume

100

Issue

10

Start / End Page

1870 / 1879

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tissue Array Analysis
  • Oncology & Carcinogenesis
  • Mice
  • Immunohistochemistry
  • Humans
  • HSP70 Heat-Shock Proteins
  • Glioma
  • Flow Cytometry
  • Endoplasmic Reticulum Chaperone BiP