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Cell Stress and Chaperones

, Volume 13, Issue 1, pp 1–10 | Cite as

The therapeutic implications of clinically applied modifiers of heat shock protein 70 (Hsp70) expression by tumor cells

  • Mathias Gehrmann
  • Jürgen Radons
  • Michael Molls
  • Gabriele MulthoffEmail author
Mini Review

Abstract

Evidence that membrane-bound and extracellular heat shock proteins (HSPs) with molecular weights of 70 and 90 kDa are potent stimulators of the immune responses has accumulated over the last decade. In this review, we discuss the modulation of Hsp70 expression, a major stress-inducible member of the HSP70 family, in the cytoplasm and on the plasma membrane of tumor cells by clinically applied interventions such as radio- and chemotherapy.

Keywords

Hsp70 Membrane expression Stress response modifiers NK cell Tumor 

Abbreviations

13-RA

13-cis-retinoic acid

ALL

acute lymphoid leukemia

AML

acute myeloid leukemia

APC(s)

antigen presenting cell(s)

APL

acute promyelocytic leukemia

ARA-CTP

arabinosyl-cytosin-triphosphate

ASA

acetyl-salicylic acid

ATRA

all-trans-retinoic acid

B-CLL

B cell chronic lymphoid leukemia

CD

cluster of differentiation (nomenclature for surface proteins of human leucocytes)

CLX

celecoxib

COX

cyclooxygenase

ER

endoplasmic reticulum

Hsp

heat shock protein

IL

interleukin

NCR

natural cytotoxicity receptor

NHL

non-Hodgkin lymphoma

NK

natural killer cell

NKG2D

C-type lectin-like immunoreceptor on NK cells

NKT cells

natural killer-like T cells

PI3K

phosphatidyl-inositol-3-phosphat kinase

PIO

pioglitazone

PIPLC

phosphatidyl-inositol-specific phospholipase C

PKC

protein kinase C

RFX

rofecoxib

SBU

sodium butyrate

TKD

14-mer Hsp70 peptide with the amino acid sequence T-K-D-N-N-L-L-G-R-F-E-L-S-G

TLR

Toll-like receptor

TNF

tumor necrosis factor

Notes

Acknowledgment

This work was supported in part by the EU-Transnet project MRTN-2004-512253, the DFG project MU1238 7/2, and the multimmune GmbH, Munich. We want to thank Prof. Graham Pockley (University of Sheffield, UK, presently Technical University Munich) for constructive suggestions and for proofreading of the manuscript.

References

  1. Abou-Issa HM, Alshafie GA, Seibert K, Koki AT, Masferrer JL, Harris RE (2001) Dose-response effects of the COX-2 inhibitor, celecoxib, on the chemoprevention of mammary carcinogenesis. Anticancer Res 21:3425–3432PubMedGoogle Scholar
  2. Altucci L, Gronemeyer H (2001) Nuclear receptors in cell life and death. Trends Endocrinol Metab 12:460–468PubMedCrossRefGoogle Scholar
  3. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442PubMedCrossRefGoogle Scholar
  4. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of Toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034PubMedCrossRefGoogle Scholar
  5. Bandyopadhyay G, Laudanski K, Li F, Lentz C, Bankey P, Miller-Graziano C (2007) Negative signalling contributes to T cell energy in trauma patients. Crit Car Med 13:794–801CrossRefGoogle Scholar
  6. Barreto A, Gonzalez JM, Kabingu E, Asea A, Fiorentino S (2003) Stress-induced release of Hsc70 form human tumors. Cell Immunol 222:97–104PubMedCrossRefGoogle Scholar
  7. Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313PubMedCrossRefGoogle Scholar
  8. Becker T, Hartl FU, Wieland F (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol 158:1277–1285PubMedCrossRefGoogle Scholar
  9. Blagosklonny MV, Fojo T (1999) Molecular effects of paclitaxel: myths and reality (a critical review). Int J Cancer 83:151–156PubMedCrossRefGoogle Scholar
  10. Botzler C, Kis K, Issels R, Multhoff G (1997) A comparison of the effects of ifosfamide vs. mafosfamide treatment on intracellular glutathione levels and immunological functions of immunocompetent lymphocyte subsets. Exp Hematol 25:338–344PubMedGoogle Scholar
  11. Botzler C, Ellwart J, Gunther W, Eissner G, Multhoff G (1999) Synergistic effects of heat and ET-18-OCH3 on membrane expression of hsp70 and lysis of leukemic K562 cells. Exp Hematol 27:470–478PubMedCrossRefGoogle Scholar
  12. Brune K, Hinz B (2004) Selective cyclooxygenase-2 inhibitors: similarities and differences. Scand J Rheumatol 33:1–6PubMedCrossRefGoogle Scholar
  13. Calderwood SK, Theriault JR, Gong J (2005) Message in a bottle: role of the 70 kDa HSP in anti-tumor immunity. Eur J Cancer 35:2518–2527Google Scholar
  14. Calderwood SK, Mambula SS, Gray PJ, Theriault JR (2007) Extracellular HSP in cell signalling. FEBS Lett 581:3689–3694Google Scholar
  15. Callari D, Sinatra F, Paravizzini G et al (2003) All-trans retinoic acid sensitizes colon cancer cells to hyperthermia cytotoxic effects. Int J Oncol 23:181–188PubMedGoogle Scholar
  16. Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM (2000) Intracellular unesterified arachidonic acid signals apoptosis. Proc Natl Acad Sci U S A 97:11280–11285PubMedCrossRefGoogle Scholar
  17. Chen X, Tao Q, Yu H, Zhang L, Cao X (2002) Tumor cell membrane-bound Hsp70 elicits antitumor immunity. Immunol Lett 84:81–87PubMedCrossRefGoogle Scholar
  18. Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedCrossRefGoogle Scholar
  19. Ciocca DR, Rozados VR, Cuello Carrion FD, Gervasoni SI, Matar P, Scharovsky OG (2003) Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin. Cell Stress Chaperones 8:26–36PubMedCrossRefGoogle Scholar
  20. Corley DA, Kerlikowske K, Verma R, Buffler P (2003) Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124:47–56PubMedCrossRefGoogle Scholar
  21. DeMaio A (2000) Heat shock proteins, oxygen radicals, and apoptosis: the conflict between protection and destruction. Crit Care Med 28:1679–1681PubMedCrossRefGoogle Scholar
  22. Dimanche-Boitrel MT, Meurette O, Rebillard A, Lacour S (2005) Role of early plasma membrane events in chemotherapy-induced cell death. Drug Resist Updat 8:5–14PubMedCrossRefGoogle Scholar
  23. Eissner G, Multhoff G, Gerbitz A, Kirchner S, Bauer S, Haffner S, Sondermann D, Andreesen R, Holler E (2002) Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide. Blood 100:334–340PubMedCrossRefGoogle Scholar
  24. Farrow DC, Vaughan TL, Hansten PD et al (1998) Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarker Prev 7:97–102Google Scholar
  25. Freemantle SJ, Spinella MJ, Dmitrovsky E (2003) Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene 22:7305–7315PubMedCrossRefGoogle Scholar
  26. Gabai VL, Meriin AB, Yaglom JA, Volloch VZ, Sherman MY (1998) Role of Hsp70 in regulation of stress-kinase JNK: implications in apoptosis and aging. FEBS Lett 438:1–4PubMedCrossRefGoogle Scholar
  27. Gehrmann M, Pfister K, Hutzler P, Gastpar R, Margulis B, Multhoff G (2002) Effects of antineoplastic agents on cytoplasmic and membrane-bound heat shock protein 70 (Hsp70) levels. Biol Chem 383:1715–1725PubMedCrossRefGoogle Scholar
  28. Gehrmann M, Schmetzer H, Eissner G, Haferlach T, Hiddemann W, Multhoff G (2003) Membrane-bound heat shock protein 70 (Hsp70) in acute myeloid leukemia: a tumor specific recognition structure for the cytolytic activity of autologous NK cells. Haematologica 88:474–476PubMedGoogle Scholar
  29. Gehrmann M, Brunner M, Pfister K, Reichle A, Kremmer E, Multhoff G (2004) Differential up-regulation of cytosolic and membrane-bound heat shock protein 70 in tumor cells by anti-inflammatory drugs. Clin Cancer Res 10:3354–3364PubMedCrossRefGoogle Scholar
  30. Gehrmann M, Marienhagen J, Eichholtz-Wirth H, Fritz E, Ellwart J, Jaattela M, Zilch T, Multhoff G (2005a) Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells. Cell Death Differ 12:38–51PubMedCrossRefGoogle Scholar
  31. Gehrmann M, Schonberger J, Zilch T, Rossbacher L, Thonigs G, Eilles C, Multhoff G (2005b) Retinoid- and sodium-butyrate-induced decrease in heat shock protein 70 membrane-positive tumor cells is associated with reduced sensitivity to natural killer cell lysis, growth delay, and altered growth morphology. Cell Stress Chaperones 10:136–146PubMedCrossRefGoogle Scholar
  32. Gendimenico GJ, Mezick JA (1993) Pharmacological effects of retinoids on skin cells. Skin Pharmacol 6(Suppl 1):24–34PubMedGoogle Scholar
  33. Gidding CE, Kellie SJ, Kamps WA, de Graaf SS (1999) Vincristine revisited. Crit Rev Oncol Hematol 29:267–287PubMedCrossRefGoogle Scholar
  34. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 121:241–246PubMedGoogle Scholar
  35. Grant S (1998) Ara-C: cellular and molecular pharmacology. Adv Cancer Res 72:197–233PubMedCrossRefGoogle Scholar
  36. Gross C, Koelch W, DeMaio A, Arispe N, Multhoff G (2003a) Cell surface-bound heat shock protein 70 (Hsp70) mediates perforin-independent apoptosis by specific binding and uptake of granzyme B. J Biol Chem 278:41173–41181PubMedCrossRefGoogle Scholar
  37. Gross C, Schmidt-Wolf IG, Nagaraj S, Gastpar R, Ellwart J, Kunz-Schughart LA, Multhoff G (2003b) Heat shock protein 70-reactivity is associated with increased cell surface density of CD94/CD56 on primary natural killer cells. Cell Stress Chaperones 8:348–360PubMedCrossRefGoogle Scholar
  38. Gross C, Hansch D, Gastpar R, Multhoff G (2003c) Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol Chem 384:267–279PubMedCrossRefGoogle Scholar
  39. Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858PubMedCrossRefGoogle Scholar
  40. Heczkova B, Slotte JP (2006) Effect of anti-tumor ether lipids on ordered domains in model membranes. FEBS Lett 580:2471–2476PubMedCrossRefGoogle Scholar
  41. Hightower L, Guidon PT (1989) Selective release from cultured mammalian cells of heat shock (stress) proteins that resemble glia-axxon transfer protein. J Cell Physiol 138:257–266PubMedCrossRefGoogle Scholar
  42. Hirakawa T, Rokutan K, Nikawa T, Kishi K (1996) Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa. Gastroenterology 111:345–357PubMedCrossRefGoogle Scholar
  43. Jaattela M (1999) Escaping cell death: survival proteins in cancer. Exp Cell Res 248:30–43PubMedCrossRefGoogle Scholar
  44. Jaattela M, Wissing D, Kokholm K, Kallunki T, Egeblad M (1998) Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases. EMBO J 17:6124–6134PubMedCrossRefGoogle Scholar
  45. Johnson TW, Anderson KE, Lazovich D, Folsom AR (2002) Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomark Prev 11:1586–1591Google Scholar
  46. Kismet K, Akay MT, Abbasoglu O, Ercan A (2004) Celecoxib: a potent cyclooxygenase-2 inhibitor in cancer prevention. Cancer Detect Prev 28:127–142PubMedCrossRefGoogle Scholar
  47. Korbelik M, Sun J, Cecic I (2005) Photodynamic therapy-induced cell surface expression and release of HSPs: relevance for tumor response. Cancer Res 65:1018–1026PubMedGoogle Scholar
  48. Krause SW, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G, Pfister K, Multhoff G (2004) Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase I trial. Clin Cancer Res 10:3699–3707PubMedCrossRefGoogle Scholar
  49. Lee CJ, Han JS, Seo CY, Park TH (2006) Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells. Apoptosis 11:401–411PubMedCrossRefGoogle Scholar
  50. Mardini IA, FitzGerald GA (2001) Selective inhibitors of cyclooxygenase-2: a growing class of anti-inflammatory drugs. Mol Interv 1:30–38PubMedCrossRefGoogle Scholar
  51. Masferrer JL, Leahy KM, Koki AT (2000) Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res 60:1306–1311PubMedGoogle Scholar
  52. Massa C, Guiducci C, Arioli I, Parenza M, Colombo MP, Melani C (2004) Enhanced efficacy of tumro cell vaccines transfected with secretable hsp70. Cancer Res 64:15023–1508CrossRefGoogle Scholar
  53. Massaro GD, Massaro D (2000) Retinoic acid treatment partially rescues failed septation in rats and in mice. Am J Physiol Lung Cell Mol Physiol 278:955–960Google Scholar
  54. Matsumoto H, Wang X, Ohnishi T (1995) Binding between wild-type p53 and hsp72 accumulated after UV and gamma-ray irradiation. Cancer Lett 92:127–133PubMedCrossRefGoogle Scholar
  55. Mollinedo F, Gajate C, Martin-Santamaria S, Gago F (2004) ET-18-OCH3 (edelfosine): a selective antitumour lipid targeting apoptosis through intracellular activation of Fas/CD95 death receptor. Curr Med Chem 11:3163–3184PubMedGoogle Scholar
  56. Multhoff G, Botzler C, Wiesnet M, Muller E, Meier T, Wilmanns W, Issels RD (1995) 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 61:272–279PubMedCrossRefGoogle Scholar
  57. Multhoff G, Botzler C, Allenbacher A, Issels R (1996) Effects of ifosfamide on immunocompetent effector cells. Cancer Immunol Immunother 42:251–254PubMedCrossRefGoogle Scholar
  58. Multhoff G, Botzler C, Jennen L, Schmidt J, Ellwart J, Issels R (1997) Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol 158:4341–4350PubMedGoogle Scholar
  59. Multhoff G, Pfister K, Botzler C, Jordan A, Scholz R, Schmetzer H, Burgstahler R, Hiddemann W (2000) Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors. Int J Cancer 88:791–797PubMedCrossRefGoogle Scholar
  60. Multhoff G, Pfister K, Gehrmann M, Hantsche lM, Gross C, Hafner M, Hiddemann W (2001) A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress Chaperones 6:337–344PubMedCrossRefGoogle Scholar
  61. Nagpal S, Thacher SM, Patel S et al (1996) Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ 7:1783–1791PubMedGoogle Scholar
  62. O’Dwyer PJ, Stevenson JP, Johnson SW (2000) Clinical pharmacokinetics and administration of established platinum drugs. Drugs 59(Suppl 4):19–27PubMedCrossRefGoogle Scholar
  63. Okami J, Yamamoto H, Fujiwara Y et al (1999) Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin Cancer Res 5:2018–2024PubMedGoogle Scholar
  64. Panayi GS, Corrigal VM (2006) Bip regulates autoimmune inflammation and tissue damage. Autoimmun Rev 5:140–142PubMedCrossRefGoogle Scholar
  65. Park DJ, Vuong PT, de Vos S, Douer D, Koeffler HP (2003) Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays. Blood 102:3727–3736PubMedCrossRefGoogle Scholar
  66. Park JE, Facciponte J, Chen X, MacDonald I, Repasky EA, Manjili MH, Wang XY, Subjeck JR (2006) Chaperoning function of stress protein grp170, a member of the HSP70 superfamily, is responsible for its immuno-adjuvant activity. Cancer Res 66:1161–1168PubMedCrossRefGoogle Scholar
  67. Parker WB, Secrist JA, Waud WR (2004) Purine nucleoside antimetabolites in development for the treatment of cancer. Curr Opin Investig Drugs 5:592–596PubMedGoogle Scholar
  68. Patti R, Gumired K, Reddanna P, Sutton LN, Phillips PC, Reddy CD (2002) Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: effect of celecoxib and rofecoxib. Cancer Lett 180:13–21PubMedCrossRefGoogle Scholar
  69. Pfister K, Radons J, Busch R, Tidball J, Pfeifer M, Freitag L, Feldman HJ, Milani V, Issels R, Multhoff G (2007) Patient survival by Hsp70 membrane-phenotype: association with different routes of metastasis. Cancer 110:926–935PubMedCrossRefGoogle Scholar
  70. Quintana FJ, Carmi P, Mor F, Cohen IR (2004) Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70 kDa or the 90 kDA HSP: immune cross-regulation with the 60 kDa HSP. Arthritis Rheum 50:3712–3720PubMedCrossRefGoogle Scholar
  71. Richter M, Weiss M, Weinberger I, Furstenberger G, Marian B (2001) Growth inhibition and induction of apoptosis in colorectal tumor cells by cyclooxygenase inhibitors. Carcinogenesis 22:17–25PubMedCrossRefGoogle Scholar
  72. Shamma A, Yamamoto H, Doki Y et al (2000) Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. Clin Cancer Res 6:1229–1238PubMedGoogle Scholar
  73. Shin BK, Wang H, Yim AM et al (2003) Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278:7607–7616PubMedCrossRefGoogle Scholar
  74. Sierra-Rivera E, Voorhees GJ, Freeman ML (1993) Gamma irradiation increases hsp-70 in Chinese hamster ovary cells. Radiat Res 135:40–45PubMedCrossRefGoogle Scholar
  75. Song AM, Bhagat L, Singh VP, Van Acker GG, Steer ML, Saluja AK (2002) Inhibition of cyclooxygenase-2 ameliorates the severity of pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol 283:G1166–G1174PubMedGoogle Scholar
  76. Srivastava PK, Menoret A, Basu S, Binder RJ, McQuade KL (1998) Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 8:657–665PubMedCrossRefGoogle Scholar
  77. Stangl S, Wortmann A, Guertler U, Multhoff G (2006) Control of metastasized pancreatic carcinomas in SCID/beige mice with human IL-2/TKD-activated NK cells. J Immunol 176:6270–6276PubMedGoogle Scholar
  78. Suzuki K, Watanabe M (1992) Augmented expression of HSP72 protein in normal human fibroblasts irradiated with ultraviolet light. Biochem Biophys Res Commun 186:1257–1264PubMedCrossRefGoogle Scholar
  79. Theriaults JR, Adachi H, Calderwood SK (2006) Role of scavenger receptors in the binding and internalization of HSP70. J Immunol 177:8604–8611Google Scholar
  80. Thun MJ, Namboodiri MM, Heath CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596PubMedCrossRefGoogle Scholar
  81. Todryk SM, Gough MJ, Pockley G (2003) Facets of Hsp70 show immunotherapeutic potentialImmunology. 110:1–9PubMedCrossRefGoogle Scholar
  82. Triantafilou M, Triantafilou K (2004) Hsp70 and Hsp90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem Soc Trans 32:636–639PubMedCrossRefGoogle Scholar
  83. Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6:130–140PubMedCrossRefGoogle Scholar
  84. Vabulas RM, Wagner H, Schild H (2002) Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol 270:169–184PubMedGoogle Scholar
  85. Wan YJ, Cai Y, Cowan C, Magee TR (2000) Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells. Cancer Lett 154:19–27PubMedCrossRefGoogle Scholar
  86. Wang Z, Fuentes CF, Shapshay SM (2002) Antiangiogenic and chemopreventive activities of celecoxib in oral carcinoma cell. Laryngoscope 112:839–843PubMedCrossRefGoogle Scholar
  87. Wang M-H, Grossmann ME, Young CYF (2004) Forced expression of Hsp70increases the secretion of Hsp70 and provides protection against tumour growth. Brit J Cancer 90:926–931PubMedCrossRefGoogle Scholar
  88. Wang XY, Arnouk H, Chen X, Kazim L, Repasky EA, Subjeck JR (2006) Extracellular targeting of ER chaperone glucose-related protein 170 enhances tumor immunity to a poorly immunogenic melanoma. J Immunol 177:1543–1551PubMedGoogle Scholar
  89. Wei YQ, Zhao X, Kariya Y, Teshigawara K, Uchida A (1995) Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells. Cancer Immunol Immunother 40:73–78PubMedCrossRefGoogle Scholar
  90. Yamazaki R, Kusunoki N, Matsuzaki T, Hashimoto S, Kawai S (2002) Selective cyclooxygenase-2 inhibitors show a differential ability to inhibit proliferation and induce apoptosis of colon adenocarcinoma cells. FEBS Lett 531:278–284PubMedCrossRefGoogle Scholar
  91. Zhang H, Huang W (2007) A 14-mer peptide form Hsp70 protein is the critical epitope which enhances NK activity against tumor cells in vivo. Immunol Invest 36:233–246PubMedCrossRefGoogle Scholar
  92. Zeng Y, Chen X, Larmonier N, Li G, Sepassi M, Marron M, Andraeansky S, Katsanis E (2006) NK cells play a key role in the antitumor immunity generated by chaperone-rich lysate vaccination. Int J Cancer 119:2624–2631PubMedCrossRefGoogle Scholar
  93. Zimmermann FB, Geinitz H, Schill S, Thamm R, Nieder C, Schratzenstaller U, Molls M (2006) Stereotactic hypofractionated radiotherapy in stage I (T1–2 N0 M0) non-small-cell lung cancer (NSCLC). Acta Oncol 45:796–801PubMedCrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2008

Authors and Affiliations

  • Mathias Gehrmann
    • 1
  • Jürgen Radons
    • 2
  • Michael Molls
    • 1
  • Gabriele Multhoff
    • 1
    Email author
  1. 1.Department of Radiotherapy and Radiooncology and Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH)–Institute of Pathology, Clinical Cooperation Group “Innate Immunity in Tumor Biology”University Hospital rechts der Isar, Technische Universität MünchenMunichGermany
  2. 2.Institute of Medical Biochemistry and Molecular BiologyUniversity of Greifswald, Clinical CenterGreifswaldGermany

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