Original Paper

Radiation and Environmental Biophysics

, Volume 49, Issue 2, pp 261-270

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Effect of tumour-cell-derived or recombinant keratinocyte growth factor (KGF) on proliferation and radioresponse of human epithelial tumour cells (HNSCC) and normal keratinocytes in vitro

  • Andrea HilleAffiliated withDepartment of Radiotherapy and Radiooncology, University Medicine Göttingen
  • , Susanne GrügerAffiliated withDepartment of Radiotherapy and Radiooncology, University Medicine Göttingen
  • , Hans ChristiansenAffiliated withDepartment of Radiotherapy and Radiooncology, University Medicine Göttingen
  • , Hendrik A. WolffAffiliated withDepartment of Radiotherapy and Radiooncology, University Medicine Göttingen
  • , Beate VolkmerAffiliated withDermatology Centre Elbeklinikum Buxtehude
  • , Jörg LehmannAffiliated withDepartment of Radiation Oncology, University of California Davis School of Medicine
  • , Wolfgang DörrAffiliated withDepartment of Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology
  • , Margret Rave-FränkAffiliated withDepartment of Radiotherapy and Radiooncology, University Medicine Göttingen Email author 

Abstract

Purpose of this work was to test the effect of tumour-cell-derived keratinocyte growth factor (KGF) or recombinant KGF (palifermin) on cell proliferation and radiation response of human HNSCC cells and normal keratinocytes in vitro. Four tumour cell cultures derived from head and neck squamous cell carcinomas, primary keratinocytes, and immortalized keratinocytes were analysed. Fibroblasts, the natural source of KGF protein, served as controls. KGF expression was observed in primary and immortalized keratinocytes, fibroblasts, and in tumour cells, while significant KGF receptor expression was only found in keratinocytes. Recombinant KGF as well as tumour-cell-derived KGF caused a significant growth stimulation and radioprotection in keratinocytes, which was abolished by a neutralizing anti-KGF antibody. This indicates that tumour-cell-derived KGF is biologically active. In the tumour cell lines, no significant growth stimulation was induced by recombinant KGF, and the neutralizing antibody did not influence tumour cell growth or radiation response. Our results indicate that the normal, paracrine KGF regulatory mechanisms, which are based on KGF receptor expression, are lost in malignant cells, with the consequence of irresponsiveness of the tumour cells to exogenous KGF. In face of the amelioration of the radiation response of normal epithelia, demonstrated in various clinical and various preclinical animal studies, recombinant KGF represents a candidate for the selective protection of normal epithelia during radio(chemo) therapy of squamous cell carcinoma.