Erythropoietin and G-csf Receptors in Human Tumor Cells: Expression and Aspects regarding Functionality

Westphal, Gabriela; Niederberger, Ellen; Blum, Christoph; Wollman, Yoram; Knoch, Tobias; Rebel, W.; Debus, Jürgen; Friedrich, E.

doi:10.1177/030089160208800214

Cited by 86 publications

(63 citation statements)

References 47 publications

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“…[18][19][20]24,[55][56][57][58][59][60][61][62] In experimental animal models of cancer, disruption of erythropoietin-erythropoietin receptor signaling in tumors was associated with an antitumor effect in xenografts of human female genital tract cancers and melanoma 58,61 and in a rodent syngeneic model of breast cancer. 19 The pathophysiologic role, if any, of erythropoietin receptor and erythropoietin coexpression in prostate cancer cells and whether exogenous recombinant erythropoietin may exert direct in vivo effects on tumor cells that express erythropoietin receptor remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin and erythropoietin receptor expression in human prostate cancer

et al. 2005

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Erythropoietin is a hematopoietic cytokine that regulates the production of red blood cells. Erythropoietin is normally produced in the adult kidney in a hypoxia-inducible manner. The recombinant form of human erythropoietin is in clinical use for the prevention and treatment of anemia that is associated with cancer and its treatment with chemoradiation therapy. A series of recent studies from our laboratory and others have reported the expression of receptors for erythropoietin in several different types of human cancer cells. In the present study, we investigated the expression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer. In clinical specimens of prostate cancer, we found abundant expression of erythropoietin receptor protein in all primary tumors examined using immunohistochemistry. Furthermore, we observed erythropoietin coexpression in prostate cancer cells by immunohistochemical analysis. To determine whether monolayer cultures of continuous cell lines derived from prostate cancer also express erythropoietin receptor and erythropoietin, we studied well-characterized hormone-responsive (LNCaP) and hormone-refractory (PC-3) prostate cancer cell lines. We performed reverse-transcription and polymerase chain reaction assays to detect erythropoietin receptor and erythropoietin mRNA transcripts, and also immunoprecipitation and immunoblotting to detect erythropoietin receptor protein expression in prostate cancer cells. These experiments revealed the expression of both erythropoietin receptor and erythropoietin in LNCaP and PC-3 cells suggesting that these prostate cancer cell lines may serve as useful experimental models for further studies of erythropoietin and erythropoietin receptor function in prostate cancer. The coexpression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer cells suggests the potential for growth regulation by erythropoietin-erythropoietin receptor in an autocrine or paracrine manner.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin and erythropoietin receptor expression in human prostate cancer

et al. 2005

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“…Epo and/or Epo receptor expression have been found in liver stromal cells and some primary hepatic tumors, and tumor cell lines as well as in Kupffer cells during regeneration [87,[89][90][91][92][93] . Still, we have not found any data on Epo expression and signaling in human cholangiocarcinoma www.wjgnet.com Smirnova OV et al JAK-STAT and cholangiocarcinoma cell leukemia-1 (mcl-1) mRNA and protein expression which is a key member of the antiapoptotic Bcl-2 protein family [107,110] .…”

Section: Erythropoietin (Epo) Jak-stat Signalingmentioning

confidence: 99%

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Smirnova¹

2007

WJG

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The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

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“…The Epo-R has been isolated in both renal cancer and other solid tumours, and is thought to play a role in disease progression (Da Silva et al, 1990;Acs et al, 2002). Similarly, in vitro studies have revealed conflicting results highlighting Epo to be both cytotoxic and proliferative in nature (Westenfelder and Baranowski, 2000;Westphal et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity

et al. 2003

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The recombinant growth factors (GFs) erythropoietin (Epo) and granulocyte-macrophage colony stimulating factor (GM-CSF) have important roles in the management of cancer patients. However, the effects of these GFs at a cellular level are not well understood. We examined the effect of GFs alone, and in combination with cytotoxic chemotherapy, in a panel of seven cell lines. Flow cytometric analysis showed varying levels of receptor expression, which correlated with phosphorylated MAPK expression. Additionally, there were also concomitant increases in BCL-2 protein levels in those cells with high levels of MAPK activation. Although culturing cells with Epo or GM-CSF did not alter cell viability by themselves, GF pretreatment in cell lines expressing higher receptor levels resulted in a reduced magnitude of cell kill following exposure to cytotoxic IC 50 concentrations of cisplatin. Subsequent co-culture with either the MEK inhibitor U0126 or the GM-CSF antagonist E21R negated this induced resistance to cytotoxic chemotherapy, confirming the importance of the GF receptor as well as MAPK in mediating these effects. These results suggest that the use of GFs during chemotherapy may be detrimental in those cancers expressing higher levels of the specific receptor. Conversely, our results also suggest that GFs are safe to use in chemotherapeutic regimens if the cancer cells do not overexpress the particular receptor.

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Erythropoietin and G-csf Receptors in Human Tumor Cells: Expression and Aspects regarding Functionality

Abstract: These results demonstrate that Epo and G-CSF did not modulate the growth rate of examined receptor-positive tumor cell lines; the presence of the Epo receptor seems not essential for cell growth of these tumor cells in cell culture.

Cited by 86 publications

References 47 publications

Erythropoietin and erythropoietin receptor expression in human prostate cancer

Erythropoietin and erythropoietin receptor expression in human prostate cancer

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity

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