Skip to main content

Advertisement

SpringerLink
Log in

Identification of the protein components of protein-bound polysaccharide (PSK) that interact with NKL cells

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

We identified the protein components of a protein-bound polysaccharide (PSK) that are responsible for the biological function of this immunomodulator in its interaction with NKL cells, an NK-derived cell line previously known to be activated by this extract, obtained from the basidiomycete Coriolus versiocolor. In addition, we show that PSK protein interacts with NKL cells through a different receptor from that used by IL-2. This was deduced from the different molecular weights of the PSK/NKL and IL-2/NKL receptor complexes. We show that PSK is composed of a highly glycosylated 12-kDa protein. Protein-bound polysaccharide interacts in vitro with an NKL receptor of approximately 48 kDa, whereas IL-2 shows a similar interaction with NKL receptor proteins of approximately 64 and 75 kDa. Our results may explain why PSK and IL-2 use completely different intracellular routes for their biological activities in NKL cells—i.e., regulating different PKC isozymes, mitogen-activated protein kinases, and nuclear transcription factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Algarra I, Collado A, Garrido F (1997) Protein-bound polysaccharide PSK abrogates more efficiently experimental metastases derived from H-2 negative than from H-2 positive fibrosarcoma tumor clones. J Exp Clin Cancer Res 16:373

    CAS  PubMed  Google Scholar 

  2. Algarra I, Garcia-Lora A, Collado A, Garrido F (1999) Differential effect of protein-bound polysaccharide (PSK) on survival of experimental murine tumors. J Exp Clin Cancer Res 18:39

    CAS  PubMed  Google Scholar 

  3. Asai K, Kato H, Hirose K, Akaogi K, Kimura S, Mukai S, Inoue M, Yamamura Y, Sano H, Sugino S, Yoshikawa T, Kondo M (2000) PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated cytotoxicity. Immunopharmacol Immunotoxicol 22:221

    CAS  PubMed  Google Scholar 

  4. Browder LW, Wilkes J, Rodenhiser DI (1992) Preparative labeling of proteins with [35S]methionine. Anal Biochem 204:85

    CAS  PubMed  Google Scholar 

  5. Fisher M, Yang LX (2002) Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res 22:1737

    CAS  PubMed  Google Scholar 

  6. Fujii T, Hisanaka T, Ogoma Y, Kondo Y (1993) Interaction of a protein-bound polysaccharide (PSK) with chicken gizzard caldesmon. Biol Pharm Bull 16:544

    CAS  PubMed  Google Scholar 

  7. Garcia-Lora A, Pedrinaci S, Garrido F (2001) Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. Cancer Immunol Immunother 50:191

    Article  CAS  PubMed  Google Scholar 

  8. Garcia-Lora A, Martinez M, Pedrinaci S, Garrido F (2003) Different regulation of PKC isoenzymes and MAPK by PSK and IL-2 in the proliferative and cytotoxic activities of the NKL human natural killer cell line. Cancer Immunol Immunother 52:59

    CAS  PubMed  Google Scholar 

  9. Kanazawa M, Mori Y, Yoshihara K, Iwadate M, Suzuki S, Endoh Y, Ohki S, Takita K, Sekikawa K, Takenoshita S (2004) Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes. Immunol Lett 15(91):229

    Article  Google Scholar 

  10. Kariya Y, Inoue N, Kihara T, Fujii M (1992) Activation of human natural killer cells by the protein bound polysaccharide PSK independently of interferon and interleukin 2. Immunol Lett 31:241

    Article  CAS  PubMed  Google Scholar 

  11. Kobayashi H, Matsunaga K, Oguchi Y (1995) Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiol Biomarkers Prev 4:275

    CAS  PubMed  Google Scholar 

  12. Kudo S, Tanaka J, Kashida H, Tamegai Y, Endo S, Yamano HO (2002) Effectiveness of immunochemotherapy with PSK, a protein-bound polysaccharide, in colorectal cancer and changes of tumor marker. Oncol Rep 9:635

    CAS  PubMed  Google Scholar 

  13. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 15(227):680

    Google Scholar 

  14. Liu F, Ooi VE, Chang ST (1997) Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci 60:763

    Article  CAS  PubMed  Google Scholar 

  15. Munemoto Y, Lida Y, Abe J, Saito H, Fujisawa K, Kasahara I, Mitsui T, Asada Y, Miura S (2002) Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: association between host or tumor factors and survival. Int J Oncol 20:403

    PubMed  Google Scholar 

  16. Munemoto Y, Iida Y, Ohata K, Saito H, Fujisawa K, Kasahara Y, Mitsui T, Asada Y, Miura S (2004) Significance of postoperative adjuvant immunochemotherapy after curative resection of colorectal cancers: identification of responders incorporating the age factor. Oncol Rep 11:623

    CAS  PubMed  Google Scholar 

  17. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 343:1122

    Article  CAS  PubMed  Google Scholar 

  18. Nio Y, Shiraishi T, Tsubono M, Morimoto H, Tseng C, Imai S, Tobe T (1991) In vitro immunomodulating effect of protein-bound polysaccharide PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer. Cancer Immunol Immunother 32:335

    CAS  PubMed  Google Scholar 

  19. Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y (2004) Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer 90:1003

    Article  CAS  PubMed  Google Scholar 

  20. Okuzawa M, Shinohara H, Kobayashi T, Iwamoto M, Toyoda M, Tanigawa N (2002) PSK, a protein-bound polysaccharide, overcomes defective maturation of dendritic cells exposed to tumor-derived factors in vitro. Int J Oncol 20:1189

    CAS  PubMed  Google Scholar 

  21. Ooi VE, Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem 7:715

    CAS  PubMed  Google Scholar 

  22. Pang ZJ, Chen Y, Zhou M, Wan J (2000) Effect of polysaccharide krestin on glutathione peroxidase gene expression in mouse peritoneal macrophages. Br J Biomed Sci 57:130

    CAS  PubMed  Google Scholar 

  23. Pedrinaci S, Algarra I, Garrido F (1999) Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. Int J Clin Lab Res 29(4):135

    Article  CAS  PubMed  Google Scholar 

  24. Robertson MJ, Cochran KJ, Cameron C, Le JM, Tantravahi R, Ritz J (1996) Characterization of a cell line, NKL, derived from an aggressive human natural killer cell leukemia. Exp Hematol 24:406

    CAS  PubMed  Google Scholar 

  25. Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K (1984) PSK. Cancer Treat Rev 11:131

    Article  CAS  Google Scholar 

  26. Voss S, Sondel P, Robb R (1992) Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2; association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R. J Exp Med 176:531

    Article  CAS  PubMed  Google Scholar 

  27. Zhang H, Morisaki T, Nakahara C, Matsunaga H, Sato N, Nagumo F, Tadano J, Katano M (2003) PSK-mediated NF-kappaB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene 10;22:2088

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank K. Shashok for improving the English in the manuscript. This work was supported by Kureha Chemical Industry, Tokyo, Japan.

Author information

Authors and Affiliations

  1. Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Avda. de las Fuerzas Armadas 2, 18014, Granada, Spain

    Eva Jiménez, Angel Garcia-Lora, Marisol Martinez & Federico Garrido

Authors
  1. Eva Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angel Garcia-Lora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marisol Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federico Garrido
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Federico Garrido.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiménez, E., Garcia-Lora, A., Martinez, M. et al. Identification of the protein components of protein-bound polysaccharide (PSK) that interact with NKL cells. Cancer Immunol Immunother 54, 395–399 (2005). https://doi.org/10.1007/s00262-004-0601-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-004-0601-1

Keywords

Search

Navigation