Erythropoietin Receptor Expression in Non-Small Cell Lung Carcinoma: A Question of Antibody Specificity

Brown, W. Mark; Maxwell, Perry; Graham, Alastair; Yakkundi, Anita; Dunlop, Elaine A.; Shi, Zhiyong; Johnston, Patrick G.; Lappin, Terence

doi:10.1634/stemcells.2006-0687

Cited by 93 publications

(65 citation statements)

References 17 publications

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“…They concluded that Epo treatment might adversely affect the prognosis of head and neck cancer patients if cancer cells express EpoRs. We strongly agree with the reservations expressed by Della Ragione and colleagues [10] concerning the specificity of the EpoR C20 antibody used in this recent study by Henke et al [9] because it has been clearly demonstrated that it cross-reacts with heat shock protein-70 [11,12].…”

Section: In Reply Terence R J Lappin a Peter Maxwell Patrick G supporting

confidence: 91%

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2007

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Section: In Reply Terence R J Lappin a Peter Maxwell Patrick G supporting

confidence: 91%

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2007

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“…In addition, currently available EPO receptor antibodies lack specificity and generally identify heat shock protein (hsp)70, a poor prognosis tumor marker [28]. Although a recent study suggested that preabsorption of the currently used EPO receptor antiserum C20 with an hsp70 peptide improved antibody specificity for plasma membrane-associated protein, the study was done using NSCLC tissue microarrays, only 30% of the tumors retained membrane staining, and no control tissue was studied to confirm antibody specificity for the EPO receptor in this system [29]. Reports using such antibodies to demonstrate EPO receptor expression in tumor cells by immunohistochemistry or immunoblotting should, therefore, be viewed with caution.…”

Section: Tumor Progression Resulting From Stimulation Of Tumor Cell Ementioning

confidence: 99%

Anemia Management in Oncology and Hematology

2009

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Anemia is frequent in cancer patients and its incidence increases with chemotherapy. The probability of requiring transfusions also increases with chemotherapy. Anemia negatively impacts survival and accentuates fatigue in cancer patients. Cancer promotes inflammatory cytokine production, which suppresses erythropoiesis and erythropoietin (EPO) production. Erythropoiesis-stimulating agents (ESAs) improve erythropoiesis and reduce transfusion needs in anemic cancer patients receiving chemotherapy. However, meta-analyses have shown an increased risk of thromboembolic (TE) events with ESA use during chemotherapy, but not increased on-study mortality or reduced overall survival. Three reasons have been proposed to explain why ESAs might have adverse effects in anemic cancer patients: tumor progression due to stimulation of tumor cell EPO receptors; increased risk of TE; and reduced survival. However, erythropoietin is not an oncogene, nor is the EPO receptor. It has also been demonstrated that erythropoietin does not stimulate tumor proliferation. Increased TE risk associated with ESAs is probably a consequence of increased blood viscosity due to excessive RBC mass elevation with concomitant plasma volume contraction, nitric oxide scavenging, and endothelial cell activation. Increased ESA dosing may also impact survival negatively because EPO contracts the plasma volume and stimulates inflammatory cytokine production independently of increasing erythropoiesis. Furthermore, transfusions themselves are associated with an increase in TE and plasma volume contraction, and these events are potentiated when ESAs are given with transfusions. An update on the management of anemia in oncology, the potential adverse events of ESAs, the benefits and risks of transfusions, and QoL are discussed in this paper. The

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“…We used the polyclonal antibody (M-20) previously shown to have a reliable specificity (Lopez et al 2011) to identify the EpoR by Western blot and immunohistochemistry, since the anti-EpoR antibody (C-20 Santa Cruz Biotech) has been reported to cross-react with HSP70, which is also highly expressed in tumor tissue (Brown et al 2007). Interestingly, the detection of an approximately 59 kDa band by Western blot using the polyclonal M-20 antibody suggested the significantly overexpressed presence of the EpoR in liver tissue during CC development, as also confirmed by RT-PCR analysis.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development

Moriconi¹,

Ramadori²,

Schultze³

et al. 2013

Z Gastroenterol

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It has been recently shown that the biological effects of erythropoietin (EPO) are not limited to the hematopoietic compartment but, as pleiotropic glycoprotein, this hormone can exert pro-angiogenic and tissue-protective functions also in a wide range of non-hematopoietic organs. The role of EPO and the effective functionality of its receptor in solid tumors are still a controversial point of debate. In the present work we analyzed the gene expression of EPO and its cognate receptor (EpoR) in a rat model of thioacetamideinduced damage and tumor. An analysis of the EPO/EpoR axis was also performed on human cholangiocarcinoma (CC) cell lines. A progressive increase of EPO and EpoR mRNA can already be observed during the fibrotic-cirrhotic development with a peak of expression rising at tumor formation (24.7 ± 9.9-fold increase and 15.5 ± 1.1-fold increase, respectively, for the two genes). Co-localization studies by immunofluorescence revealed hepatocytes in the regenerative cirrhotic nodules (Hep Par-1 ? ) and in the dysplastic bile duct cells (CK19 ? ) as the major EPO producers in this specific condition. The same cell populations, together with endothelial cells, exhibited an increased expression of EpoR, although all the non-parenchymal cell populations in the liver exhibited modest basal mRNA levels. Challenging human CC cells, Mz-Cha-2, with a combination of EPO and SCF resulted in a synergistic effect on the gene expression of EPO, CyclinD1 and PCNA. This study suggests that the autocrine and paracrine release of endogenous EPO in the microenvironment may contribute to the development and maintenance of the CC possibly in cooperation with other signaling pathways.

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Erythropoietin Receptor Expression in Non-Small Cell Lung Carcinoma: A Question of Antibody Specificity

Abstract: STEM CELLS 2007;25:718 -722

Cited by 93 publications

References 17 publications

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Anemia Management in Oncology and Hematology

Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development

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