title: Functional significance of erythropoietin in renal cell carcinoma.
abstract: One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion.
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland at Princess Alexandra Hospital, Building 33, Brisbane, Queensland, 4102, Australia. c.morais@uq.edu.au
authors.forename: Christudas
authors.initials: C
authors.lastname: Morais
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: David A
authors.initials: DA
authors.lastname: Vesey
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
mesh_terms: D000740:Anemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004921:Erythropoietin / Q000009:adverse effects / Q000378:metabolism*; D006397:Hematinics / Q000009:adverse effects; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects; D012307:Risk Factors; D015398:Signal Transduction; D059016:Tumor Microenvironment; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
chemical_list: C554270:EPO protein, human; D006397:Hematinics; D051793:Hypoxia-Inducible Factor 1; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human