Abstract
BackgroundSeveral 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.MethodsHuman 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.ResultsThere 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-648) contains supplementary material, which is available to authorized users.
Highlights
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
We have previously shown that Epo in combination with surgical trauma can stimulate growth of xenotransplanted tumours [13], while there was no growth stimulating effect of Epo alone
We showed that the combination effect of Epo and surgery did not involve a direct interaction between Epo and the tumour cells [14]
Summary
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. In 2003, a study [8] revealed significantly worse outcome for HNSCC patients treated with Epo. Other studies involving Epo administration during treatment of non-small-cell carcinoma of the lung (NSCLC) [7] and breast cancer [9] showed lower survival rates for Epo treated patients. Other studies involving Epo administration during treatment of non-small-cell carcinoma of the lung (NSCLC) [7] and breast cancer [9] showed lower survival rates for Epo treated patients These results raised the concern that Epo might stimulate tumour growth. Several studies on the use of Epo to ameliorate anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival
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