Erythropoietin Stimulates Tumor Growth via EphB4

Pradeep, Sunila; Huang, Jie; Mora, Edna; Nick, Alpa M.; Cho, Min Soon; Wu, Sherry Y.; Noh, Kyunghee; Pecot, Chad V.; Rupaimoole, Rajesha; Stein, Martin; Brock, Stephan; Wen, Yunfei; Xiong, Chiyi; Gharpure, Kshipra M.; Hansen, Jean M.; Nagaraja, Archana S.; Previs, Rebecca A.; Vivas‐Mejía, Pablo E.; Han, Hee Dong; Hu, Wei; Mangala, Lingegowda S.; Zand, Behrouz; Stagg, Loren; Ladbury, John E.; Özpolat, Bülent; Alpay, S. Neslihan; Nishimura, Masato; Stone, Rebecca L.; Matsuo, Koji; Armaiz-Peña, Guillermo N.; Dalton, Heather J.; Danes, Christopher G.; Goodman, Blake W.; Rodríguez-Aguayo, Cristian; Krüger, Carola; Schneider, Armin; Haghpeykar, Shyon; Jaladurgam, Padmavathi; Hung, Mien‐Chie; Coleman, Robert L.; Liu, Jinsong; Li, Chun; Urbauer, Diana L.; López-Berestein, Gabriel; Jackson, David B.; Sood, Anil K.

doi:10.1016/j.ccell.2015.09.008

Cited by 80 publications

(74 citation statements)

References 47 publications

(49 reference statements)

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“…Another study by Pradeep et al . reported that EphB4 receptor promotes tumor growth and progression via stimulation of STAT3 signaling26. We noticed reduced expression of phosphorylated and total STAT3 in PDX tumors following sEphB4-HSA treatment with radiation.…”

Section: Discussionmentioning

confidence: 49%

“…Enhanced apoptosis is one of the key anti-tumor responses mediated by EphB4 targeting and radiation325262728. In caspase-3/7 assay, we observed a significant increase in apoptosis (~28%) in Fadu cells transfected with EphB4-siRNA and 4 Gy dose of radiation compared to radiation alone at 96 h (Fig.…”

Section: Resultsmentioning

confidence: 72%

“…Enhanced apoptosis is one of the main mechanisms underlying the anti-tumorigenic effects of sEphB4-HSA treatment325263940. Reports suggest that DNA damage is a causative factor of apoptosis following radiation24.…”

Section: Discussionmentioning

confidence: 99%

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Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Sharma

Oweida

Griego

et al. 2016

Sci Rep

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Members of the Eph family of receptor tyrosine kinases have been implicated in a wide array of human cancers. The EphB4 receptor is ubiquitously expressed in head and neck squamous cell carcinoma (HNSCC) and has been shown to impart tumorigenic and invasive characteristics to these cancers. In this study, we investigated whether EphB4 receptor targeting can enhance the radiosensitization of HNSCC. Our data show that EphB4 is expressed at high to moderate levels in HNSCC cell lines and patient-derived xenograft (PDX) tumors. We observed decreased survival fractions in HNSCC cells following EphB4 knockdown in clonogenic assays. An enhanced G2 cell cycle arrest with activation of DNA damage response pathway and increased apoptosis was evident in HNSCC cells following combined EphB4 downregulation and radiation compared to EphB4 knockdown and radiation alone. Data using HNSCC PDX models showed significant reduction in tumor volume and enhanced delay in tumor regrowth following sEphB4-HSA administration with radiation compared to single agent treatment. sEphB4-HSA is a protein known to block the interaction between the EphB4 receptor and its ephrin-B2 ligand. Overall, our findings emphasize the therapeutic relevance of EphB4 targeting as a radiosensitizer that can be exploited for the treatment of human head and neck carcinomas.

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Section: Discussionmentioning

confidence: 49%

Section: Resultsmentioning

confidence: 72%

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Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Sharma

Oweida

Griego

et al. 2016

Sci Rep

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“…Human Breast Cancer cell line MDA-MB-231 and human epithelial ovarian cancer cell lines SKOV3ip1, HeyA8, A2274, A2780, OVCAR5, OVCAR8, RMG2, and IGROV1 were maintained as described previously (Pradeep et al, 2015). Human immortalized umbilical endothelial cells (RF24) and human dermal microvascular endothelial cells were grown in MEM medium with supplements (sodium pyruvate, non-essential amino acids, MEM vitamins, and glutamine; Life Technologies, Grand Island, NY).…”

Section: Matrials and Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as previously reported (Pradeep et al, 2015, Haemmerle et al, 2017). Cell lysate of RF24 cells were treated with human recombinant EGFL6 protein or anti-EGFL6 antibodies and checked for activation of PI3kinase and AKT signaling by using anti-human EGFL6, PI3kinase, and AKT antibodies followed by secondary antibodies conjugated with horseradish peroxidase.…”

Section: Matrials and Methodsmentioning

confidence: 99%

Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis

et al. 2017

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SUMMARY Angiogenesis inhibitors are important for cancer therapy, but clinically approved anti-angiogenic agents have shown only modest efficacy and can compromise wound healing. This necessitates development of novel anti-angiogenesis therapies. Here, we show significantly increased EGFL6 expression in tumor- versus wound or normal endothelial cells. Using a series of in vitro and in vivo studies with orthotopic and genetically engineered mouse models, we demonstrate the mechanisms by which EGFL6 stimulates tumor angiogenesis. In contrast to its antagonistic effects on tumor angiogenesis, EGFL6 blockage did not affect normal wound healing. These findings have significant implications for development of anti-angiogenesis therapies.

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Carbon Dots as a Potential Therapeutic Agent for the Treatment of Cancer‐Related Anemia

Wang

Zhang

et al. 2022

Advanced Materials

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Due to the adverse effects of erythropoietin (EPO) on cancer patient survival, it is necessary to develop new agents that can be used to efficiently manage and treat cancer‐related anemia. In this study, novel distinctive carbon dots, J‐CDs, derived from jujube are designed, synthesized, and characterized. Based on the obtained results, this material comprises sp2 and sp3 carbon atoms, as well as oxygen/nitrogen‐based groups, and it specifically promotes the proliferation of erythroid cells by stimulating the self‐renewal of erythroid progenitor cells in vitro and in vivo. Moreover, J‐CDs have no discernible effects on tumor proliferation and metastasis, unlike EPO. Transcriptome profiling suggests that J‐CDs upregulate the molecules involved in hypoxia response, and they also significantly increase the phosphorylation levels of STAT5, the major transducer of signals for erythroid progenitor cell proliferation. Overall, this study demonstrates that J‐CDs effectively promote erythrocyte production without affecting tumor proliferation and metastasis; thus, they may be promising agents for the treatment of cancer‐related anemia.

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Erythropoietin Stimulates Tumor Growth via EphB4

Cited by 80 publications

References 47 publications

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis

Carbon Dots as a Potential Therapeutic Agent for the Treatment of Cancer‐Related Anemia

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