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Open Access Highly Accessed Research article

Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma

Gustaf Lindgren1*, Lars Ekblad2, Johan Vallon-Christersson2, Elisabeth Kjellén2, Maria Gebre-Medhin2 and Johan Wennerberg1

Author Affiliations

1 Department of Otorhinolaryngology/Head and Neck Surgery, Lund University Hospital, SE-22185 Lund, Sweden

2 Department of Oncology, Lund University Hospital, Lund, Sweden

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BMC Cancer 2014, 14:648  doi:10.1186/1471-2407-14-648

Published: 2 September 2014

Abstract

Background

Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.

Methods

Human tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3.

Results

There was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3.

Conclusions

Our results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery.

This further suggests that the decreased survival during erythropoietin treatment might be due to inhibition of apoptosis.

Keywords:
Erythropoietin; Head and neck cancer; Surgery; Apoptosis; Wound healing; Xenograft