Erythropoietin and cancer: the unintended consequences of anemia correction.

Until 1990, erythropoietin (EPO) was considered to have a single biological purpose and action, the stimulation of red blood cell growth and differentiation. Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitro and the identification of EPO receptors (EPORs) on neuronal cells. We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones.

Human selenium binding protein-1 (hSP56) is a negative regulator of HIF-1α and suppresses the malignant characteristics of prostate cancer cells.

In the present study, we demonstrate that ectopic expression of 56-kDa human selenium binding protein-1 (hSP56) in PC-3 cells that do not normally express hSP56 results in a marked inhibition of cell growth in vitro and in vivo. Down-regulation of hSP56 in LNCaP cells that normally express hSP56 results in enhanced anchorage-independent growth. PC-3 cells expressing hSP56 exhibit a significant reduction of hypoxia inducible protein (HIF)-1α protein levels under hypoxic conditions without altering HIF-1α mRNA (HIF1A) levels.

Human erythropoietin increases the pro-angiogenic potential of A2780 ovarian adenocarcinoma cells under hypoxic conditions.

Erythropoietin (Epo) is a key regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of the recombinant protein, it is widely used to treat various types of anemias, including that associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Our previous studies confirmed the presence of Epo receptors (EpoRs) in ovarian adenocarcinoma cell lines and demonstrated that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling and increased paclitaxel resistance.

Location and the functionality of erythropoietin receptor(s) in A2780 cells.

Erythropoietin (Epo) is a critical regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of a recombinant protein, it is widely used to treat various forms of anemia, including that associated with cancer and with the myelosuppressive effects of chemotherapy. Studies of ovarian cancer cell lines have demonstrated the presence of the Epo receptor (EpoR), but there are disagreements regarding its localization and functionality in these cells.

Erythropoietin and erythropoiesis stimulating agents.

Erythropoietin (EPO) is the main hormonal regulator of red blood cell production. Recombinant EPO has become the leading drug for treatment of anaemia from a variety of causes; however, it is sometimes misused in sport with the aim of improving performance and endurance. This paper presents an introductory overview of EPO, its receptor, and a variety of recombinant human EPOs/erythropoiesis stimulating agents (ESAs) available on the market (e.

Differentially expressed genes associated with cisplatin resistance in human ovarian adenocarcinoma cell line A2780.

Ovarian cancer cells are usually initially sensitive to platinum-based chemotherapy, such as cisplatin (CDDP), but typically become resistant over time. Such drug resistance is a serious impediment to successful disease treatment, and the molecular mechanisms responsible for resistance are not fully understood. In search of novel mechanisms that may lead to the development of CDDP chemoresistance, we used subtractive hybridization to identify differentially expressed genes in CDDP resistant CP70 and C200 cells vs.

Report on isoelectric focusing trial of erythropoietin profiling in two cancer patients during chemotherapy and darbepoetin treatment.

The level of erythropoietin, main regulator of erythropoiesis, is affected by hypoxia, anaemia, application of recombinant erythropoietin, chemotherapy and others. Isoelectric focusing (IEF) combined with double immunobloting is a method that enables distinct analysis of endogenous and recombinant erythropoietin isoforms. Aim of our study was to set up analysis of treatment effects on the pattern of endogenous erythropoietin in anaemic breast cancer patient.

An erythropoietin autocrine/paracrine axis modulates the growth and survival of human prostate cancer cells.

Erythropoietin receptors have been identified on a variety of cancer-derived cell lines and primary cancer cells, including those of prostate cancer. The functional status of these extrahematopoietic erythropoietin receptors remains a matter of some dispute. The publication of several important clinical trials suggesting a direct effect of erythropoietin on the growth and survival of primary tumors adds further importance to the question of whether erythropoietin receptors on cancer cells are functional.

Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner.

Reduced expression of the 56-kDa human selenium binding protein-1 (hSP56) has been reported in many types of human malignancies, including prostate, lung, ovarian, thyroid and colorectal cancers. hSP56 also has been implicated in selenium-dependent cell growth inhibition. However, the molecular basis of hSP56's function has not been elucidated.

Erythropoietin inhibits apoptosis induced by photodynamic therapy in ovarian cancer cells.

Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established.

The erythropoietin receptor in normal and cancer tissues.

The hormone erythropoietin (EPO) is essential for the survival, proliferation and differentiation of the erythrocytic progenitors. The EPO receptor (EPO-R) of erythrocytic cells belongs to the cytokine class I receptor family and signals through various protein kinases and STAT transcription factors. The EPO-R is also expressed in many organs outside the bone marrow, suggesting that EPO is a pleiotropic anti-apoptotic factor.

Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel-resistant phenotype.

Erythropoietin (Epo), a glycoprotein hormone that is the principal regulator of erythropoiesis, is known to act also on nonhematopoietic cell types. Epo receptors have been reported on several normal and neoplastic human cells and tissues, including ovarian cancer cells. We found that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling, evidenced by increased peak levels of phospho-Erk1/2 and increased paclitaxel resistance.

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.

Variability in the immunodetection of His-tagged recombinant proteins.

Labeling of recombinant proteins with polypeptide fusion partners, or affinity tagging, is a useful method to facilitate subsequent protein purification and detection. Poly-histidine tags (His-tags) are among the most commonly used affinity tags. We report strikingly variable immunodetection of two His-tagged recombinant human erythropoietins (Epo): wild type Epo (Epo(wt)) and Epo containing an R103A mutation (Epo(R103A)).

Erythropoietin stimulates growth and STAT5 phosphorylation in human prostate epithelial and prostate cancer cells.

Background: Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells.

Methods: RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level.

Apoptosis-linked gene-2 connects the Raf-1 and ASK1 signalings.

Raf-1 plays important roles in cell proliferation, differentiation, and survival. However, the unique and essential function of Raf-1 is anti-apoptotic. The molecules that mediate Raf-1's anti-apoptotic function are not known.

Measurement of hemoglobin in long-term fixed erythroid cells: application development for cell science experiments in microgravity.

Studying the effects of microgravity on cell differentiation will enhance our understanding of fundamental biology and is indispensable for a sustained space program. Rauscher murine erythroleukemic cells were chosen as a model system to study erythroid cell differentiation aboard the International Space Station because these cells undergo differentiation in response to the natural inducer, erythropoietin, as well as various chemical-inducers. We have now developed a method to quantify hemoglobin in Rauscher cells after weeks of fixation and storage required for such space biology experiments.

Erythropoietin regulation of Raf-1 and MEK: evidence for a Ras-independent mechanism.

Stimulation of the erythropoietin (EPO) receptor triggers a cascade of signaling events. We reported that EPO upregulates c-myc expression through 2 pathways in BaF3-EpoR cells--a phosphatidylinositol 3-kinase (PI3K) pathway operating on transcriptional initiation and a Raf-1-mitogen-activated protein kinase (MAPK) pathway affecting elongation. We now show that EPO induces phosphorylation of Raf-1 at serine 338 and within the carboxy-terminal domain, resulting in an electrophoretic mobility change (hyperphosphorylation).

Pleiotrophic actions of erythropoietin.

Erythropoietin is the prime regulator of red blood cell production. However, recent evidence suggests that the hormone has multiple effects outside the hematopoietic system. Functional receptors have been identified on a wide variety of normal and malignant cell types, and numerous biologic effects of the hormone on these cells have been observed both in vitro and in vivo.