Conversion of glioma cells to glioma stem-like cells by angiocrine factors

Jun Kyum Kim; Hye Min Jeon; Hee Young Jeon; Se Yeong Oh; Eun Jung Kim; Xiong Jin; Se Hoon Kim; Sung Hak Kim; Xun Jin; Hyunggee Kim

doi:10.1016/j.bbrc.2017.02.076

Conversion of glioma cells to glioma stem-like cells by angiocrine factors

Jun Kyum Kim, Hye Min Jeon, Hee Young Jeon, Se Yeong Oh, Eun Jung Kim, Xiong Jin, Se Hoon Kim, Sung Hak Kim, Xun Jin, Hyunggee Kim

Department of Pathology

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation.

Original language	English
Pages (from-to)	1013-1018
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	496
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2017.02.076
Publication status	Published - 2018 Feb 19

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning ( 2011-0017544 and 2016R1D1A1B03931941 ), from Next-Generation Biogreen21 Program ( PJ01107701 ), and from General Program of the National Natural Science Foundation of China (nos. 81572891 ). We appreciate Ji-Hyun Kim for providing graphic abstract.

Publisher Copyright:
© 2017 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2017.02.076

Cite this

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title = "Conversion of glioma cells to glioma stem-like cells by angiocrine factors",

abstract = "Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation.",

author = "Kim, {Jun Kyum} and Jeon, {Hye Min} and Jeon, {Hee Young} and Oh, {Se Yeong} and Kim, {Eun Jung} and Xiong Jin and Kim, {Se Hoon} and Kim, {Sung Hak} and Xun Jin and Hyunggee Kim",

note = "Funding Information: This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning ( 2011-0017544 and 2016R1D1A1B03931941 ), from Next-Generation Biogreen21 Program ( PJ01107701 ), and from General Program of the National Natural Science Foundation of China (nos. 81572891 ). We appreciate Ji-Hyun Kim for providing graphic abstract. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

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language = "English",

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AU - Kim, Jun Kyum

AU - Jeon, Hye Min

AU - Jeon, Hee Young

AU - Oh, Se Yeong

AU - Kim, Eun Jung

AU - Jin, Xiong

AU - Kim, Se Hoon

AU - Kim, Sung Hak

AU - Jin, Xun

AU - Kim, Hyunggee

N1 - Funding Information: This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning ( 2011-0017544 and 2016R1D1A1B03931941 ), from Next-Generation Biogreen21 Program ( PJ01107701 ), and from General Program of the National Natural Science Foundation of China (nos. 81572891 ). We appreciate Ji-Hyun Kim for providing graphic abstract. Publisher Copyright: © 2017 Elsevier Inc.

PY - 2018/2/19

Y1 - 2018/2/19

N2 - Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation.

AB - Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation.

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Conversion of glioma cells to glioma stem-like cells by angiocrine factors

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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