Data from Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages Article Swipe
Wei Yuan
,
Qian Zhang
,
Danling Gu
,
Chenfei Lu
,
Deobrat Dixit
,
Ryan C. Gimple
,
Yisu Gao
,
Jiancheng Gao
,
Daqi Li
,
Danyan Shan
,
Lang Hu
,
Lu Li
,
Yangqing Li
,
Shusheng Ci
,
Hao You
,
Linping Yan
,
Kexin Chen
,
Ningwei Zhao
,
Chuanhai Xu
,
Jianyun Lan
,
Dong Liu
,
Junxia Zhang
,
Zhumei Shi
,
Qiulian Wu
,
Kailin Yang
,
Linjie Zhao
,
Zhixin Qiu
,
Deguan Lv
,
Wei Gao
,
Hui Yang
,
Fan Lin
,
Qianghu Wang
,
Jianghong Man
,
Chaojun Li
,
Weiwei Tao
,
Sameer Agnihotri
,
Xu Qian
,
Stephen C. Mack
,
Nu Zhang
,
Yongping You
,
Jeremy N. Rich
,
Guan Sun
,
Xiuxing Wang
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.6779678
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1078-0432.c.6779678
Purpose:The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state.Experimental Design:We performed an integrative multi-omics analyses of RNA sequencing, GBM mRNA expression datasets, immune signatures, and epigenetic profiling to define the specific genes expressed in the mesenchymal GSC subsets. We then used patient-derived GSCs and a xenograft murine model to investigate the mechanisms of tumor-intrinsic and extrinsic factor to maintain the mesenchymal state of GSCs and induce TAM polarization.Results:We identified that CXCL8 was preferentially expressed and secreted by mesenchymal GSCs and activated PI3K/AKT and NF-κB signaling to maintain GSC proliferation, survival, and self-renewal through a cell-intrinsic mechanism. CXCL8 induced signaling through a CXCR2–JAK2/STAT3 axis in TAMs, which supported an M2-like TAM phenotype through a paracrine, cell-extrinsic pathway. Genetic- and small molecule–based inhibition of these dual complementary signaling cascades in GSCs and TAMs suppressed GBM tumor growth and prolonged survival of orthotopic xenograft-bearing mice.Conclusions:CXCL8 plays critical roles in maintaining the mesenchymal state of GSCs and M2-like TAM polarization in GBM, highlighting an interplay between cell-autonomous and cell-extrinsic mechanisms. Targeting CXCL8 and its downstream effectors may effectively improve GBM treatment.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1078-0432.c.6779678
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385666502
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4385666502Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/1078-0432.c.6779678Digital Object Identifier
- Title
-
Data from Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated MacrophagesWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-08Full publication date if available
- Authors
-
Wei Yuan, Qian Zhang, Danling Gu, Chenfei Lu, Deobrat Dixit, Ryan C. Gimple, Yisu Gao, Jiancheng Gao, Daqi Li, Danyan Shan, Lang Hu, Lu Li, Yangqing Li, Shusheng Ci, Hao You, Linping Yan, Kexin Chen, Ningwei Zhao, Chuanhai Xu, Jianyun Lan, Dong Liu, Junxia Zhang, Zhumei Shi, Qiulian Wu, Kailin Yang, Linjie Zhao, Zhixin Qiu, Deguan Lv, Wei Gao, Hui Yang, Fan Lin, Qianghu Wang, Jianghong Man, Chaojun Li, Weiwei Tao, Sameer Agnihotri, Xu Qian, Stephen C. Mack, Nu Zhang, Yongping You, Jeremy N. Rich, Guan Sun, Xiuxing WangList of authors in order
- Landing page
-
https://doi.org/10.1158/1078-0432.c.6779678Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1158/1078-0432.c.6779678Direct OA link when available
- Concepts
-
Mesenchymal stem cell, Cancer research, Tumor microenvironment, Paracrine signalling, Biology, STAT3, PI3K/AKT/mTOR pathway, Tumor progression, Stem cell, Reprogramming, Signal transduction, Cell biology, Cell, Receptor, Gene, Genetics, Tumor cellsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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