Does erythropoietin have a dark side? Epo signaling and cancer cells.
Erythropoietin (Epo) stimulates red blood cell production by docking with its cognate receptor on the erythroid progenitor cell and triggering an array of signaling pathways that inhibit apoptosis and promote cell proliferation and differentiation. In its pharmaceutical forms, epoetin and darbepoetin, Epo is widely used to treat various anemias, including those associated with cancer. The Epo receptor is also expressed by nonhematopoietic cells, including cancer cells, and Epo exhibits a "tissue-protective" effect on nonhematopoietic tissues, possibly mediated through a novel heteroreceptor, blocking apoptosis induced by a variety of insults. The unexpected results of several clinical studies in which Epo was used to treat cancer patients have now raised the question of a potential direct growth-promoting action of Epo on cancer cells.
Sytkowski
Arthur J
AJ
Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. asytkows@bidmc.harvard.edu
D000740:Anemia / Q000188:drug therapy; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D053648:Cytokine Receptor Common beta Subunit / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000009:adverse effects / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D053614:Janus Kinase 2 / Q000502:physiology; D020935:MAP Kinase Signaling System; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017467:Receptors, Erythropoietin / Q000145:classification / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
C115876:CSF2RB protein, human; D053648:Cytokine Receptor Common beta Subunit; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D004921:Erythropoietin; D019869:Phosphatidylinositol 3-Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt