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Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling

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Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling. / Qu, Yi; Oyan, Anne Margrete; Liu, Runhui; Hua, Yaping; Zhang, Jigang; Hovland, Randi; Popa, Mihaela; Liu, Xiaojun; Brokstad, Karl A; Simon, Ronald; Molven, Anders; Lin, Biaoyang; Zhang, Wei-dong; McCormack, Emmet; Kalland, Karl-Henning; Ke, Xi-Song.

in: CANCER RES, Jahrgang 73, Nr. 23, 01.12.2013, S. 7090-100.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Qu, Y, Oyan, AM, Liu, R, Hua, Y, Zhang, J, Hovland, R, Popa, M, Liu, X, Brokstad, KA, Simon, R, Molven, A, Lin, B, Zhang, W, McCormack, E, Kalland, K-H & Ke, X-S 2013, 'Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling', CANCER RES, Jg. 73, Nr. 23, S. 7090-100. https://doi.org/10.1158/0008-5472.CAN-13-1560

APA

Qu, Y., Oyan, A. M., Liu, R., Hua, Y., Zhang, J., Hovland, R., Popa, M., Liu, X., Brokstad, K. A., Simon, R., Molven, A., Lin, B., Zhang, W., McCormack, E., Kalland, K-H., & Ke, X-S. (2013). Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling. CANCER RES, 73(23), 7090-100. https://doi.org/10.1158/0008-5472.CAN-13-1560

Vancouver

Qu Y, Oyan AM, Liu R, Hua Y, Zhang J, Hovland R et al. Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling. CANCER RES. 2013 Dez 1;73(23):7090-100. https://doi.org/10.1158/0008-5472.CAN-13-1560

Bibtex

@article{7d9c8c268e474fd08899d390c772930f,
title = "Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling",
abstract = "How prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor-initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting.",
keywords = "Animals, Cell Proliferation, Humans, Interleukin-6, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Mice, Transgenic, Neoplastic Stem Cells, Prostatic Neoplasms, Reactive Oxygen Species, STAT3 Transcription Factor, Signal Transduction, Spheroids, Cellular, Tumor Cells, Cultured",
author = "Yi Qu and Oyan, {Anne Margrete} and Runhui Liu and Yaping Hua and Jigang Zhang and Randi Hovland and Mihaela Popa and Xiaojun Liu and Brokstad, {Karl A} and Ronald Simon and Anders Molven and Biaoyang Lin and Wei-dong Zhang and Emmet McCormack and Karl-Henning Kalland and Xi-Song Ke",
year = "2013",
month = dec,
day = "1",
doi = "10.1158/0008-5472.CAN-13-1560",
language = "English",
volume = "73",
pages = "7090--100",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

RIS

TY - JOUR

T1 - Generation of prostate tumor-initiating cells is associated with elevation of reactive oxygen species and IL-6/STAT3 signaling

AU - Qu, Yi

AU - Oyan, Anne Margrete

AU - Liu, Runhui

AU - Hua, Yaping

AU - Zhang, Jigang

AU - Hovland, Randi

AU - Popa, Mihaela

AU - Liu, Xiaojun

AU - Brokstad, Karl A

AU - Simon, Ronald

AU - Molven, Anders

AU - Lin, Biaoyang

AU - Zhang, Wei-dong

AU - McCormack, Emmet

AU - Kalland, Karl-Henning

AU - Ke, Xi-Song

PY - 2013/12/1

Y1 - 2013/12/1

N2 - How prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor-initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting.

AB - How prostate cancer is initiated remains a topic of debate. In an effort to establish a human model of prostate carcinogenesis, we adapted premalignant human prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly generated D5HS efficiently formed large subcutaneous tumors and subsequent metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere formation were confirmed by neutralizing antibody, chemical inhibitors, and fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS) produced upon protein depletion was required for the activation of IL-6/STAT3 in D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis of human prostate cells was further examined in xenograft tumors and verified by limiting dilution implantations. Collectively, we have for the first time established human prostate tumor-initiating cells based on physiologic adaption. The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate carcinogenesis shed new light on this relationship and define therapeutic targets in this setting.

KW - Animals

KW - Cell Proliferation

KW - Humans

KW - Interleukin-6

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Nude

KW - Mice, Transgenic

KW - Neoplastic Stem Cells

KW - Prostatic Neoplasms

KW - Reactive Oxygen Species

KW - STAT3 Transcription Factor

KW - Signal Transduction

KW - Spheroids, Cellular

KW - Tumor Cells, Cultured

U2 - 10.1158/0008-5472.CAN-13-1560

DO - 10.1158/0008-5472.CAN-13-1560

M3 - SCORING: Journal article

C2 - 24101153

VL - 73

SP - 7090

EP - 7100

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 23

ER -