Erythropoietin and erythropoietin receptor expression in human prostate cancer

Arcasoy, Murat O.; Amin, Khalid; Vollmer, Robin T.; Jiang, Xiaohong; Demark‐Wahnefried, Wendy; Haroon, Zishan A.

doi:10.1038/modpathol.3800288

Cited by 67 publications

(56 citation statements)

References 63 publications

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“…Several mechanisms of EPO involvement in tumor progression have been suggested: EPO increases EPOR expression in preexisting tumor cells, thereby increasing tumor growth and metastasis, or directly promotes tumor vascular angiogenesis (6,(8)(9)(10). In this study, we showed that EPO increases LEC density and tumor metastasis in lymph nodes.…”

Section: Discussionsupporting

confidence: 49%

“…Although the exact mechanism of EPO-induced tumor progression remains to be understood, several mechanisms of EPO-induced tumor progression have been proposed. EPO may increase EPO receptor (EPOR) expression in preexisting tumor cells, thereby promoting tumor metastasis (6,(8)(9)(10). It increases the growth of tumors lacking EPOR through tumor angiogenesis (11).…”

Section: Introductionmentioning

confidence: 99%

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Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

et al. 2011

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Cancer therapy often produces anemia, which is treated with erthropoietin (EPO) to stimulate erythrocyte production. However, concerns have recently arisen that EPO treatment may promote later tumor metastasis and mortality. The mechanisms underlying such effects are unknown, but it is clear that EPO has pleiotropic effects in cell types other than hematopoietic cells. In this study, we investigated how EPO affects lymphangiogenesis and lymph node tumor metastasis in mouse models of breast cancer and melanoma. In these models, EPO increased lymph node lymphangiogenesis and lymph node tumor metastasis in a manner associated with increased migration, capillary-like tube formation, and doseand time-dependent proliferation of human lymphatic endothelial cells. EPO increased sprouting of these cells in a thoracic duct lymphatic ring assay. These effects were abrogated by cotreatment with specific inhibitors of phosphoinositide 3-kinase or mitogen-activated protein kinase, under conditions in which EPO increased Akt and extracellular signal-regulated kinase 1/2 phosphorylation. Intraperitoneal administration of EPO stimulated peritoneal lymphangiogenesis, and systemic treatment of EPO increased infiltration of CD11b þ macrophages in tumor-draining lymph nodes. Finally, EPO increased VEGF-C expression in lymph node-derived CD11b þ macrophages as well as in bone marrow-derived macrophages in a dose-and time-dependent manner. Our results establish that EPO exerts a powerful lymphangiogenic function and can drive both lymph node lymphangiogenesis and nodal metastasis in tumor-bearing animals. Cancer Res; 71(13); 4506-17. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

et al. 2011

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“…Following the detection of expression of Epo and its receptor on multiple cell types, it has become clear that Epo has pleiotropic effects extending well beyond the maintenance of red cell mass (3). In recent years, multiple investigators have documented the presence of EpoR expression in numerous tumor cell lines and carcinomata (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) but the specificity of commercially available EpoR antibodies has been questioned (15,16). Functional studies are needed to determine whether EpoR activation modifies tumor cell growth.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin-Induced Activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK Pathways Promotes Malignant Cell Behavior in a Modified Breast Cancer Cell Line

Shi

Hodges

Dunlop

et al. 2010

Molecular Cancer Research

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Erythropoietin (Epo), the major regulator of erythropoiesis, and its cognate receptor (EpoR) are also expressed in nonerythroid tissues, including tumors. Clinical studies have highlighted the potential adverse effects of erythropoiesis-stimulating agents when used to treat cancer-related anemia. We assessed the ability of EpoR to enhance tumor growth and invasiveness following Epo stimulation. A benign noninvasive rat mammary cell line, Rama 37, was used as a model system. Cell signaling and malignant cell behavior were compared between parental Rama 37 cells, which express few or no endogenous EpoRs, and a modified cell line stably transfected with human EpoR (Rama 37-28). The incubation of Rama 37-28 cells with pharmacologic levels of Epo led to the rapid and sustained increases in phosphorylation of signal transducers and activators of transcription 5, Akt, and extracellular signal-regulated kinase. The activation of these signaling pathways significantly increased invasion, migration, adhesion, and colony formation. The Epo-induced invasion capacity of Rama 37-28 cells was reduced by the small interfering RNA-mediated knockdown of EpoR mRNA levels and by inhibitors of the phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways with adhesion also reduced by Janus-activated kinase 2/signal transducers and activators of transcription 5 inhibition. These data show that Epo induces phenotypic changes in the behavior of breast cancer cell lines and establishes links between individual cell signaling pathways and the potential for cancer spread. Mol Cancer Res; 8(4); 615-26. ©2010 AACR.

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“…Erythropoietin (Epo), a principal cytokine involved in erythropoiesis, has been reported to promote the growth of malignant tumors by binding to its receptor (EpoR) through both autocrine stimulation of malignant cells themselves and paracrine route to the feeding microvessels due to the expression of both transcripts for Epo and EpoR mRNA in very many cancers [1][2][3][4] and for EpoR mRNA in the human endothelial cells of vein and artery [5]. However, there is controversy over the EpoR in cancer patients to be functional to develop their malignancies.…”

Section: Introductionmentioning

confidence: 99%

Constitutively Active Soluble Form of Erythropoietin Receptor Suppresses Growth and Angiogenesis of Xenografts of Transfected Cancer Cell Lines

Yasuda¹,

Maeda²,

Hara³

et al. 2011

JCT

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Erythropoietin and erythropoietin receptor expression in human prostate cancer

Cited by 67 publications

References 63 publications

Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

Erythropoietin-Induced Activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK Pathways Promotes Malignant Cell Behavior in a Modified Breast Cancer Cell Line

Constitutively Active Soluble Form of Erythropoietin Receptor Suppresses Growth and Angiogenesis of Xenografts of Transfected Cancer Cell Lines

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