Stimulation of Breast Tumor Cell Proliferative Recovery by the Peptide Hormone Erythropoietin
Abstract
Recent clinical trials have demonstrated that breast cancer patients receiving chemotherapy who were also treated with erythropoietin (EPO) had a shortened lifespan compared to patients receiving chemotherapy alone. We believe that these outcomes may be a result of EPO interfering with the effectiveness of chemotherapy either by inducing cytoprotective signaling pathways through the EPO receptor, which had been identified on breast tumor cells and/or stimulating growth of dormant breast tumor cells. Our studies in cell culture, however, failed to detect stimulation of breast tumor cell growth after treatment of breast tumor cells with erythropoietin, interference with the effectiveness of chemotherapeutic drugs including adriamycin, taxol and tamoxifen or attenuation of drug-induced senescence arrest. The EPO receptor was clearly active in breast tumor cells, based on signaling through JNK, ERK and p38 kinase pathways. However, EPO failed to activate Akt or STAT 5 signaling and in fact, STAT 5 expression was not detected. We conclude that the lack of protection by EPO may be related to failure to active Akt or STAT 5 signaling. Companion studies in leukemia cells indicate that chemotherapeutic agents have the ability to suppress EPO signaling. Consequently, the influence of EPO in the clinical trials described above is likely to have another basis, such as stimulation of the invasion and/or metastatic capacity of breast tumor cells or interference with drug delivery to the tumors, possibly by increasing interstitial fluid pressure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA457796
Entities
People
- David A. Gewirtz
Organizations
- Virginia Commonwealth University