Inhibition of erythropoietin signalling destroys xenografts of ovarian anduterine cancers in nude mice

We have recently shown that malignant tumours from the ovary and uterus exp ressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation o f Epo signal in tumour blocks induced death of malignant cells and capillar y endothelial cells in vitro (Yasuda et al, submitted). These in vitro resu lts prompted us to examine the effect of Epo-signal withdrawal on tumours i n vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and Ep oR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transpl ants. At 12 h, 1, 7 or 14 days after the injection, all transplants were re sected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells thr ough apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline in jection or needle insertion showed well-developed tumour masses. This Epo r esponse pathway will have profound implications for our understanding of th e development and progression of malignant tumours and for the use of Epo-s ignal deprivation as an effective therapy. (C) 2001 Cancer Research Campaig n http://www.bjcancer.com.