Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2020; 12(11): 1396-1409
Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1396
Effect of conditioned medium from neural stem cells on glioma progression and its protein expression profile analysis
Gui-Long Zhang, Cheng Qian, Shi-Zhen Zhang, Yong-Hua Tuo, Bai-Yun Zeng, Yun-Xiang Ji, Ye-Zhong Wang
Gui-Long Zhang, Cheng Qian, Shi-Zhen Zhang, Yong-Hua Tuo, Bai-Yun Zeng, Yun-Xiang Ji, Ye-Zhong Wang, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
Gui-Long Zhang, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province China
Author contributions: Zhang GL, Qian C, and Zhang SZ designed and performed the experiments; Ji YX and Wang YZ contributed to data analysis; Zhang SZ, Tuo YH, and Zeng BY performed the experiments; Zhang GL, Qian C, and Zhang SZ wrote the paper, Ji YX and Wang YZ edited the manuscript; all authors have approved the final manuscript; Zhang GL, Qian C, and Zhang SZ contributed equally to this work.
Supported by China Postdoctoral Science Foundation, No. 2020M672592 and No. 2019TQ0071.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Affiliated Zhongda Hospital of Southeast University.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ye-Zhong Wang, MD, PhD, Chairman, Chief Doctor, Professor, Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 East Changgang Road, Haizhu District, Guangzhou 510260, Guangdong Province, China. wangyezhong@gzhmu.edu.cn
Received: June 1, 2020
Peer-review started: June 1, 2020
First decision: August 22, 2020
Revised: September 4, 2020
Accepted: September 25, 2020
Article in press: September 25, 202
Published online: November 26, 2020
Abstract
BACKGROUND

Emerging evidence suggests that the spread of glioma to the subventricular zone (SVZ) is closely related to glioma recurrence and patient survival. Neural stem cells (NSCs) are the main cell type in the SVZ region and exhibit tumor-homing ability.

AIM

To evaluate the effects of conditioned medium (CM) derived from SVZ NSCs on the cancer-related behaviors of glioma cells.

METHODS

The characteristics of SVZ hNSCs were identified by immunofluorescence. The normoxic-hNSC-CM and hypoxic-hNSC-CM (3% O2, oxygen-glucose deprived [OGD] culturing) were collected from 80%-90% confluent SVZ NSCs in sterile conditions. The CCK8 and Transwell assays were used to compare and evaluate the effects of normoxic-CM and hypoxic-CM on glioma proliferation and invasion. Then proteins secreted from SVZ NSCs into the CM were investigated by mass spectrometry, and the potential effects of candidate protein NCAN in the regulation of glioma progression were examined by CCK8 and Transwell assays.

RESULTS

The CM from SVZ NSCs significantly increased the proliferation and invasion of glioma cells, particularly the CM from OGD NSCs induced under hypoxic conditions. Furthermore, the secreted protein neurocan (NCAN) in CM from OGD NSCs was identified by proteomic analysis. NCAN was expressed in glioma cells and played regulatory roles in mediating the progression of glioma cells mainly via the Rho/Rho-associated protein kinase pathway.

CONCLUSION

Our study identified a potential interactive mechanism between SVZ NSCs and glioma cells, in which SVZ NSCs promote glioma progression via the secreted protein NCAN. These findings suggested that exploring the CM derived from cells could be a novel strategy for optimizing treatments and that NCAN derived from SVZ NSCs may be a potential new target in glioma progression.

Keywords: Neural stem cells, Glioma, Conditioned medium, NCAN, Hypoxia, Protein

Core Tip: The cell communications or crosstalk between glioma cells and non-glioma cells in the tumor microenvironment plays dominant roles in tumor therapy. The subventricular zone (SVZ) neural stem cells (NSCs) have been shown to be closely associated with glioma progression and recurrence. Interestingly, the conditioned medium (CM) from SVZ NSCs significantly promoted glioma cell proliferation and invasion, with oxygen-glucose deprived NSC-CM showing enhanced effects. Furthermore, the secreted protein NCAN presented in oxygen-glucose deprived NSC-CM played important roles in the progression of glioma cells mainly via the Rho/Rho-associated protein kinase pathway. Overall, this study provided important insights into the potential therapeutic application of NCAN derived from SVZ NSCs in the treatment of glioma.