Tumor Biology

, Volume 34, Issue 2, pp 743–748 | Cite as

Effects of heat stress on the level of heat shock protein 70 on the surface of hepatocellular carcinoma Hep G2 cells: implications for the treatment of tumors

  • Naizhong Cui
  • Yongping Xu
  • Zhenhui Cao
  • Fanxing Xu
  • Peng Zhang
  • Liji Jin
Research Article

Abstract

The ability to distinguish tumor cells from normal cells is vital to allow the immune system to selectively destroy tumor cells. In order to find an effective marker, we used enzyme-linked immunosorbent assay, immunocytochemistry, immunofluorescence, and flow cytometry to investigate the effects of heat stress on the amount of heat shock protein 70 on the surface of tumor cells (Hep G2 cells). Heat shock protein 70 is the major stress-induced heat shock protein found on the surface of tumor cells. Our results indicate that the percentage of Hep G2 cells with a detectable level of heat shock protein 70 on their cell surface increased significantly (P < 0.05) following heat stress at 42 °C for 2 h (up to 1.92 times the level before heat treatment). The detectable level of heat shock protein 70 on the surface of Hep G2 cells reached its peak 12 h after treatment. However, the fluorescent intensity of stressed and unstressed Hep G2 cells was not significantly different (P > 0.05). The increase in the level of heat shock protein 70 on the surface of tumor cells following heat stress could provide a basis for finding novel immunotoxins as targets for drug action and may have application to be used in conjunction with hyperthermia in the treatment of tumors.

Keywords

Cell surface proteins Heat stress Heat shock protein 70 Hep G2 cells 

Notes

Acknowledgments

We thank Dr. Alan K Chang (Dalian University of Technology, Dalian, China) for critical discussion and correction of the manuscript.

Conflicts of interest

None

References

  1. 1.
    Parcellier A, Gurbuxani S, Schmitt E, Solary E, Garrido C. Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun. 2003;304:505–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Garrido C, Gurbuxani S, Ravagnan L, Kroemer G. Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun. 2001;286:433–42.PubMedCrossRefGoogle Scholar
  3. 3.
    Javid B, MacAry PA, Lehner PJ. Structure and function: heat shock proteins and adaptive immunity. J Immunol. 2007;179:2035–40.PubMedGoogle Scholar
  4. 4.
    Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci. 2006;31:164–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Badowska-Kozakiewicz AM, Malicka E. Immunohistochemical evaluation of expression of heat shock proteins HSP70 and HSP90 in mammary gland neoplasms in bitches. Pol J Vet Sci. 2012;15:209–14.PubMedGoogle Scholar
  6. 6.
    Jaattela M. Escaping cell death: survival proteins in cancer. Exp Cell Res. 1999;248:30–43.PubMedCrossRefGoogle Scholar
  7. 7.
    Multhoff G, Botzler C, Wiesnet M, Müller E, Meier T, Wilmanns W, et al. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995;61:272–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, et al. Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem. 2003;278:7607–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Zheng H, Dai J, Stoilova D, Li Z, et al. Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity. J Immunol. 2001;167:6731–5.PubMedGoogle Scholar
  10. 10.
    Chen X, Tao Q, Yu H, Zhang L, Cao X. Tumor cell membrane-bound heat shock protein 70 elicits antitumor immunity. Immunol Lett. 2002;84:81–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Niyazi M, Maihoefer C, Krause M, Rödel C, Budach W, Belka C. Radiotherapy and “new” drugs—new side effects? Radiat Oncol. 2011;6:177.PubMedCrossRefGoogle Scholar
  12. 12.
    Bai XF, Liu J, Li O, Zheng P, Liu Y. Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes. J Clin Invest. 2003;111:1487–96.PubMedGoogle Scholar
  13. 13.
    Vega VL, Rodríguez-Silva M, Frey T, Gehrmann M, Diaz JC, Steinem C. Heat shock protein70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J Immunol. 2008;180:4299–307.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Naizhong Cui
    • 1
  • Yongping Xu
    • 1
  • Zhenhui Cao
    • 1
  • Fanxing Xu
    • 1
  • Peng Zhang
    • 2
  • Liji Jin
    • 1
  1. 1.Ministry of Education Center for Food Safety of Animal OriginSchool of Life Science and Biotechnology, Dalian University of TechnologyDalianChina
  2. 2.Liaoning Provincial Key Laboratory of HydrobiologyCollege of Life Science and Technology, Dalian Ocean UniversityDalianChina

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