Advanced

No direct effects of erythropoietin beta on a head and neck squamous cell carcinoma cell line which is growth stimulated in vivo.

Sasaki, Yutaka Y LU ; Kjellén, Elisabeth LU ; Mineta, Hiroyuki; Wennerberg, Johan LU and Ekblad, Lars LU (2009) In Acta oncologica (Stockholm, Sweden) 48. p.1062-1069
Abstract
Introduction. Erythropoiesis-stimulating agents (ESAs) are used in cancer therapy to reverse anaemia. It has been suggested that ESAs might improve treatment outcome by reducing tumour hypoxia, but ESAs might also increase tumour growth. In this work, the effect of recombinant human erythropoietin (rHuEpo) beta was investigated on a human head and neck squamous carcinoma cell (HNSCC) line in vitro. The cell line was previously growth stimulated in combination with surgery in a xenograft model and the investigation was initiated to see if rHuEpo directly affects the tumour cell line, alone or in combination with cell stress, or if the in vivo effect should be attributed to secondary effects. Material and methods. The cell line LU-HNSCC-7... (More)
Introduction. Erythropoiesis-stimulating agents (ESAs) are used in cancer therapy to reverse anaemia. It has been suggested that ESAs might improve treatment outcome by reducing tumour hypoxia, but ESAs might also increase tumour growth. In this work, the effect of recombinant human erythropoietin (rHuEpo) beta was investigated on a human head and neck squamous carcinoma cell (HNSCC) line in vitro. The cell line was previously growth stimulated in combination with surgery in a xenograft model and the investigation was initiated to see if rHuEpo directly affects the tumour cell line, alone or in combination with cell stress, or if the in vivo effect should be attributed to secondary effects. Material and methods. The cell line LU-HNSCC-7 was grown in vitro and treated with rHuEpo alone or in combination with radiation, cisplatin, hypoxia or tumour extracts. The expression of the Epo receptor (EpoR) was investigated by western blotting after one- and two-dimensional electrophoresis, RT-PCR and through analysis of the effect on EpoR signalling. Results. The cell line was shown not to express EpoR. Furthermore, it was only possible to detect a minor effect on cell growth (1.4 times over control, p<0.001) under specific conditions and at supra-pharmacological concentrations of rHuEpo beta. No effect was detected on cell migration. None of the cell stressing treatments could enhance the minor growth stimulatory effect of rHuEpo beta. Discussion. The conclusion is that rHuEpo beta does not stimulate tumour growth of the investigated cell line through a direct interaction with tumour cells. We hypothesise that interactions with stromal cells and the stimulation of wound healing responses might, at least partly, explain the negative effects of ESA administration during cancer treatment. We propose that EpoR expression in HNSCC tumour cells might not be a good marker for prediction of ESA induced worsening of outcomes after cancer treatment. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta oncologica (Stockholm, Sweden)
volume
48
pages
1062 - 1069
publisher
Taylor & Francis
external identifiers
  • WOS:000271228400015
  • PMID:19412811
  • Scopus:70350060348
ISSN
1651-226X
DOI
10.1080/02841860902913553
language
English
LU publication?
yes
id
ef10f59d-3cc7-4e16-a487-41c4d7d41751 (old id 1412736)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19412811?dopt=Abstract
date added to LUP
2009-06-01 10:51:50
date last changed
2016-10-13 04:32:56
@misc{ef10f59d-3cc7-4e16-a487-41c4d7d41751,
  abstract     = {Introduction. Erythropoiesis-stimulating agents (ESAs) are used in cancer therapy to reverse anaemia. It has been suggested that ESAs might improve treatment outcome by reducing tumour hypoxia, but ESAs might also increase tumour growth. In this work, the effect of recombinant human erythropoietin (rHuEpo) beta was investigated on a human head and neck squamous carcinoma cell (HNSCC) line in vitro. The cell line was previously growth stimulated in combination with surgery in a xenograft model and the investigation was initiated to see if rHuEpo directly affects the tumour cell line, alone or in combination with cell stress, or if the in vivo effect should be attributed to secondary effects. Material and methods. The cell line LU-HNSCC-7 was grown in vitro and treated with rHuEpo alone or in combination with radiation, cisplatin, hypoxia or tumour extracts. The expression of the Epo receptor (EpoR) was investigated by western blotting after one- and two-dimensional electrophoresis, RT-PCR and through analysis of the effect on EpoR signalling. Results. The cell line was shown not to express EpoR. Furthermore, it was only possible to detect a minor effect on cell growth (1.4 times over control, p&lt;0.001) under specific conditions and at supra-pharmacological concentrations of rHuEpo beta. No effect was detected on cell migration. None of the cell stressing treatments could enhance the minor growth stimulatory effect of rHuEpo beta. Discussion. The conclusion is that rHuEpo beta does not stimulate tumour growth of the investigated cell line through a direct interaction with tumour cells. We hypothesise that interactions with stromal cells and the stimulation of wound healing responses might, at least partly, explain the negative effects of ESA administration during cancer treatment. We propose that EpoR expression in HNSCC tumour cells might not be a good marker for prediction of ESA induced worsening of outcomes after cancer treatment.},
  author       = {Sasaki, Yutaka Y and Kjellén, Elisabeth and Mineta, Hiroyuki and Wennerberg, Johan and Ekblad, Lars},
  issn         = {1651-226X},
  language     = {eng},
  pages        = {1062--1069},
  publisher    = {ARRAY(0x911da10)},
  series       = {Acta oncologica (Stockholm, Sweden)},
  title        = {No direct effects of erythropoietin beta on a head and neck squamous cell carcinoma cell line which is growth stimulated in vivo.},
  url          = {http://dx.doi.org/10.1080/02841860902913553},
  volume       = {48},
  year         = {2009},
}