Effect of erythropoietin on human tumor growth in xenograft models

Kataoka, Motoyuki; Moriya, Yoichiro; Moriguchi, Yoshiyuki; Iwai, Toshiki; Fujimoto-Ouchi, Kaori; Shirane, Masatoshi; Kondoh, Kumiko; Mori, Kazushige

doi:10.3892/mmr_00000224

Cited by 5 publications

(5 citation statements)

References 28 publications

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“…Indeed, some in vitro studies have demonstrated that Epo enhances tumor proliferation [Westenfelder and Baranowski, ; Acs et al, ; Yasuda et al, ; Feldman et al, ]. However, others have demonstrated that no effects of Epo on tumor growth were observed in vitro [Dunlop et al, ; Jeong et al, ], and in vivo [Kataoka et al, ]. Our current study failed to reveal any stimulatory effects of Epo on tumor growth, however, we did find that Epo inhibits PCa cell apoptosis.…”

Section: Discussioncontrasting

confidence: 67%

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

et al. 2013

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Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta-analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk.

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Section: Discussioncontrasting

confidence: 67%

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

et al. 2013

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“…However, those results are in conflict with results from other groups who reported no effect on the same pathways using the same or similar cell types 80,91,223,232,233,259,285. Interestingly, there are several reports where rHuEpo had no effects on phosphorylation of JAK2 or STAT5, but did have effects on ERK phosphorylation 271,272,276,284,286–288.…”

Section: Is Functional Epor Expressed In Tumor Cells?contrasting

confidence: 59%

The effect of erythropoietin on normal and neoplastic cells

Elliott¹,

Sinclair²

2012

BTT

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Erythropoietin (Epo) is an essential hormone that binds and activates the Epo receptor (EpoR) resident on the surface of erythroid progenitor cells, thereby promoting erythropoiesis. Recombinant human erythropoietin has been used successfully for over 20 years to treat anemia in millions of patients. In addition to erythropoiesis, Epo has also been reported to have other effects, such as tissue protection and promotion of tumor cell growth or survival. This became of significant concern in 2003, when some clinical trials in cancer patients reported increased tumor progression and worse survival outcomes in patients treated with erythropoiesis-stimulating agents (ESAs). One of the potential mechanisms proffered to explain the observed safety issues was that functional EpoR was expressed in tumors and/or endothelial cells, and that ESAs directly stimulated tumor growth and/or antagonized tumor ablative therapies. Since then, numerous groups have performed further research evaluating this potential mechanism with conflicting data and conclusions. Here, we review the biology of endogenous Epo and EpoR expression and function in erythropoiesis, and evaluate the evidence pertaining to the expression of EpoR on normal nonhematopoietic and tumor cells.

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“…Furthermore, EPO may exert indirect effects on T cell functions via Ter cells and Ter cell-produced ARTN, such as diminished tumor cell killing capacity by T cells. These findings implicate an indirect effect of EPO on cancer treatment outcomes, which differs from previous studies that focused on the direct action of EPO on tumor cells (62).…”

Section: Discussioncontrasting

confidence: 99%

Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity

Hou

Liang

et al. 2021

Sci. Transl. Med.

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Tumor-induced CD45−Ter119+CD71+ erythroid progenitor cells, termed “Ter cells,” promote tumor progression by secreting artemin (ARTN), a neurotrophic peptide that activates REarranged during Transfection (RET) signaling. We demonstrate that both local tumor ionizing radiation (IR) and anti–programmed death ligand 1 (PD-L1) treatment decreased tumor-induced Ter cell abundance in the mouse spleen and ARTN secretion outside the irradiation field in an interferon- and CD8+ T cell–dependent manner. Recombinant erythropoietin promoted resistance to radiotherapy or anti–PD-L1 therapies by restoring Ter cell numbers and serum ARTN concentration. Blockade of ARTN or potential ARTN signaling partners, or depletion of Ter cells augmented the antitumor effects of both IR and anti–PD-L1 therapies in mice. Analysis of samples from patients who received radioimmunotherapy demonstrated that IR-mediated reduction of Ter cells, ARTN, and GFRα3, an ARTN signaling partner, were each associated with tumor regression. Patients with melanoma who received immunotherapy exhibited favorable outcomes associated with decreased expression of GFRα3. These findings demonstrate an out-of-field, or “abscopal,” effect mediated by adaptive immunity, which is induced during local tumor irradiation. This effect, in turn, governs the therapeutic effects of radiation and immunotherapy. Therefore, our results identify multiple targets to potentially improve outcomes after radiotherapy and immunotherapy.

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Effect of erythropoietin on human tumor growth in xenograft models

Cited by 5 publications

References 28 publications

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

The effect of erythropoietin on normal and neoplastic cells

Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity

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