Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma

Weiwei Tao, Chengwei Chu, Wenchao Zhou, Zhi Huang, Kui Zhai, Xiaoguang Fang, Qian Huang, Aili Zhang, Xiuxing Wang, Xingjiang Yu, Haidong Huang, Qiulian Wu, Andrew E. Sloan, Jennifer S. Yu, Xiaoxia Li, George R. Stark, Jeremy N. Rich and Shideng Bao ()
Additional contact information
Weiwei Tao: Lerner Research Institute, Cleveland Clinic
Chengwei Chu: Lerner Research Institute, Cleveland Clinic
Wenchao Zhou: Lerner Research Institute, Cleveland Clinic
Zhi Huang: Lerner Research Institute, Cleveland Clinic
Kui Zhai: Lerner Research Institute, Cleveland Clinic
Xiaoguang Fang: Lerner Research Institute, Cleveland Clinic
Qian Huang: Lerner Research Institute, Cleveland Clinic
Aili Zhang: Lerner Research Institute, Cleveland Clinic
Xiuxing Wang: University of California, San Diego
Xingjiang Yu: Lerner Research Institute, Cleveland Clinic
Haidong Huang: Lerner Research Institute, Cleveland Clinic
Qiulian Wu: University of California, San Diego
Andrew E. Sloan: University Hospitals, Case Western Reserve University
Jennifer S. Yu: Lerner Research Institute, Cleveland Clinic
Xiaoxia Li: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine
George R. Stark: Lerner Research Institute, Cleveland Clinic
Jeremy N. Rich: University of California, San Diego
Shideng Bao: Lerner Research Institute, Cleveland Clinic

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt‐induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner. Importantly, inhibition of Wnt/β-catenin-WISP1 signaling by carnosic acid (CA) suppresses GBM tumor growth. Collectively, these data demonstrate that WISP1 plays critical roles in maintaining GSCs and tumor-supportive TAMs in GBM, indicating that targeting Wnt/β-catenin-WISP1 signaling may effectively improve GBM treatment and the patient survival.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16827-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16827-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16827-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().