Skip to main content
Log in

The expressions of intrinsic and extrinsic apoptotic pathway proteins in neutrophils of oral cavity cancer patients: a preliminary study

  • Short Communication
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Introduction:

The biological availability and activity of polymorphonuclear neutrophils (PMNs) are regulated by their short life span, which can be additionally shortened by a malignant process. The signaling pathways leading to apoptotic PMN death are classified in two categories: the intrinsic and the extrinsic. In the present study the expressions of proteins participating in the extrinsic apoptotic pathway (DR5, FADD, caspase-8 activity) and the intensity of apoptosis of PMNs from patients with cancer of the oral cavity were examined. The expression of proteins participating in the intrinsic pathway (Bax and Mcl-1) were also examined in these cells. The results can be helpful in explaining the reasons for the decreased activity of these cells in oral cavity cancer patients.

Materials and Methods:

The examinations were carried out in patients with squamous cell carcinoma of the oral cavity before and after treatment. The expressions of all the proteins were measured in neutrophils and, for comparison, in autologous peripheral blood mononuclear cells (PBMCs). Western blot analysis was used to assay the expressions of DR5, FADD, Bax, and Mcl-1 in cell lysates. The apoptosis level was determined by flow cytometry and caspase-8 activity by colorimetric assay.

Results:

A lack of changes in DR5 expression associated with increased FADD protein expression and caspase-8 activity accompanied the accelerated apoptosis rates in the PMNs of the patients before treatment. Decreased expression of anti-apoptotic Mcl-1 protein was associated with an unchanged expression of pro-apoptotic Bax protein. There were no such changes in the patients PBMCs. Increased expression of Mcl-1 in the PMNs of the patients following surgical treatment was found.

Conclusion:

The acceleration of the apoptosis of PMNs of oral cavity cancer patients before treatment is dependent on both the intrinsic and extrinsic pathways.

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

Access this article

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

Instant access to the full article PDF.

References

  • Almasan A, Ashkenazi A (2003) Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev 14: 337–348

    Article  PubMed  CAS  Google Scholar 

  • Clohessy JG, Zhuang J, de Boer J et al (2006) Mcl-1 interacts with truncated bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis. J Biol Chem 281: 5750–5759

    Article  PubMed  CAS  Google Scholar 

  • Di Carlo E, Forni G, Lollini P et al (2001) The intriguing role of polymorphonuclear neutrophils in antitumor reactions.. Blood 97: 339–345

    Article  PubMed  CAS  Google Scholar 

  • Edwards SW, Derouet M, Howse M et al (2004) Regulation of neutrophils apoptosis by Mcl-1. Biochem Soc Trans 32: 489–492

    Article  PubMed  CAS  Google Scholar 

  • Gastman BR, Atarshi Y, Reichert TE et al (1999) Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res 59: 5356–5364

    PubMed  CAS  Google Scholar 

  • Han J, Goldstein LA, Gastman BR et al (2006) Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. J Biol Chem 281: 10153–10163

    Article  PubMed  CAS  Google Scholar 

  • Jablonska E, Jablonski J, Marcinczyk M et al (2008) The release of soluble forms of TRAIL and DR5 by neutrophils of oral cavity cancer patients. Folia Histochem Cytobiol 46: 177–183

    Article  PubMed  CAS  Google Scholar 

  • Jablonska E, Puzewska W, Grabowska Z et al (2005) VEGF, IL-18 and NO production by neutrophils and their serum levels in patients with oral cavity cancer. Cytokine 30: 93–99

    Article  PubMed  CAS  Google Scholar 

  • Kamohara H, Matsuyama W, Shimozato O et al (2004) Regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in human neutrophils. Immunology 111: 186–194

    Article  PubMed  CAS  Google Scholar 

  • Koga Y, Matsuzaki A, Suminoe A et al (2004) Neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL): a novel mechanism of antitumor effect by neutrophils. Cancer Res 64: 1037–1043

    Article  PubMed  CAS  Google Scholar 

  • Maianski NA, Maianski AN, Kuijpers TW et al (2004) Apoptosis of neutophils. Acta Haematol 111: 56–66

    Article  PubMed  CAS  Google Scholar 

  • Moudling DA, Quayle JA, Hart CA et al (1998) Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 92: 2495–2502

    Google Scholar 

  • Simon HU (2003) Neutrophil apoptosis pathways and their modifications in inflammation. Immunol Rev 193: 101–110

    Article  PubMed  CAS  Google Scholar 

  • Sobin LH, Wittekind C (1997) UICC TNM classification of malignant tumours, 5th edn. Springer, Berlin

    Google Scholar 

  • Sprick MR, Walczak H (2004) The interplay between the Bcl-2 family and death receptor-mediated apoptosis. Biochim Biophys Acta 1644: 125–132

    Article  PubMed  CAS  Google Scholar 

  • Stoppacciaro A, Melani C, Parenza M et al (1993) Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma. J Exp Med 178: 151–161

    Article  PubMed  CAS  Google Scholar 

  • Wang S, El-Deiry W (2003) TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 22: 8628–8633

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ewa Jabłońska.

About this article

Cite this article

Jabłońska, E., Garley, M. & Jabłoński, J. The expressions of intrinsic and extrinsic apoptotic pathway proteins in neutrophils of oral cavity cancer patients: a preliminary study. Arch. Immunol. Ther. Exp. 57, 229–234 (2009). https://doi.org/10.1007/s00005-009-0023-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-009-0023-z

Keywords

Navigation