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 Hille, Susanne Grüger, Hans Christiansen, Hendrik A. Wolff, Beate Volkmer, Jörg Lehmann, Wolfgang Dörr, Margret Rave-Fränk

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalRadiation and Environmental Biophysics
Volume49
Issue number2
DOIs
StatePublished - May 2010

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Fibroblast Growth Factor 7
Keratinocytes
tumor
tumors
Epithelial Cells
cells
Neoplasms
Radiation
In Vitro Techniques
effect
epithelium
fibroblasts
Epithelium
Growth
Fibroblasts
antibodies
stimulation
antibody
radiation
cancer

ASJC Scopus subject areas

  • Biophysics
  • Environmental Science(all)
  • Radiation

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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. / Hille, Andrea; Grüger, Susanne; Christiansen, Hans; Wolff, Hendrik A.; Volkmer, Beate; Lehmann, Jörg; Dörr, Wolfgang; Rave-Fränk, Margret.

In: Radiation and Environmental Biophysics, Vol. 49, No. 2, 05.2010, p. 261-270.

Research output: Contribution to journalArticle

Hille, Andrea ; Grüger, Susanne ; Christiansen, Hans ; Wolff, Hendrik A. ; Volkmer, Beate ; Lehmann, Jörg ; Dörr, Wolfgang ; Rave-Fränk, Margret. / 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. In: Radiation and Environmental Biophysics. 2010 ; Vol. 49, No. 2. pp. 261-270.
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