lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

SARI, a Novel Regulator of Glioma Microenvironment by Inhibiting CXCR4+ Myeloid-Derived Suppressor Cells Recruitment

37 Pages Posted: 21 May 2019

See all articles by Xin Zhang

Xin Zhang

Sichuan University - State Key Laboratory of Biotherapy; Southern Medical University - Nanfang Hospital

Lei Dai

Sichuan University - State Key Laboratory of Biotherapy

Gang Shi

Sichuan University - State Key Laboratory of Biotherapy

Jie Deng

Sichuan University - State Key Laboratory of Biotherapy

Qiang Luo

Sichuan University - Department of Radiology

Qian Xie

Sichuan University - West China Hospital

Lin Cheng

Sichuan University - State Key Laboratory of Biotherapy

Chunlei Li

Sichuan University - State Key Laboratory of Biotherapy

Yi Lin

Sichuan University - State Key Laboratory of Biotherapy

Qingnan Wang

Sichuan University - State Key Laboratory of Biotherapy

Yi Liu

Sichuan University - State Key Laboratory of Biotherapy

Ping Fan

Sichuan University - West China Hospital

Hantao Zhang

Sichuan University - State Key Laboratory of Biotherapy

Xiaolan Su

Sichuan University - State Key Laboratory of Biotherapy

Shuang Zhang

Sichuan University - Cancer Center

Yang Yang

Sichuan University - State Key Laboratory of Biotherapy

Xun Hu

Sichuan University - West China Hospital

Qiyong Gong

Sichuan University - Huaxi MR Research Center (HMRRC)

Dechao Yu

Sichuan University - State Key Laboratory of Biotherapy

Yuquan Wei

Sichuan University - State Key Laboratory of Biotherapy; Sichuan University - Cancer Center; Sichuan University - National Collaborative Innovation Center for Biotherapy

Hongxin Deng

Sichuan University - State Key Laboratory of Biotherapy; Sichuan University - Cancer Center; Sichuan University - National Collaborative Innovation Center for Biotherapy

More...

Abstract

Background: Glioblastoma multiforme (GBM) is one of the most common and lethal types of human primary brain tumours. SARI (Suppressor of AP-1 regulated by interferon) functions as a tumour suppressor in various cancers. However, the role of SARI in regulating the tumour microenvironment remains unknown.

Methods: An intracranial glioma model in nude mice, which we monitored by magnetic resonance imaging (MRI) and 3D micro-CT, were eastablished to exaim the function of SARI in glioma growth and metastasis. The underlying mechanisms of SARI function were determined by flow cytometry, immunofluerence staining, and in vitro assay. Glioma tissue microarray was employed to investigate the expression and predictive role of SARI.

Findings: SARI inhibits glioma tumour growth and metastasis by inhibiting the recruitment of MDSCs in intracranial and subcutaneous glioma. Ectopic expression of SARI efficiently inhibited intracranial and subcutaneous glioma growth as evidenced by MRI and 3D micro-CT. Mechanistically, SARI inhibits the recruitment of CXCR4+ MDSCs into the glioma microenvironment by inhibiting HIF1-α expression and SDF-1α transcription. Notably, the attenuation of SDF-1α/CXCR4 signalling could revert the effect of SARI on the inhibition of glioma progression. Furthermore, tissue microarray staining indicated that SARI expression inversely correlates with poor clinical outcomes in glioma patients.

Interprepation: SARI is a novel regulator of tumour microenvironment and a potential therapeutic and predictive target protein in glioma patients.

Funding: This study was supported by the National Natural Science Foundation of China Program grant (no. 81772939) and the National Key R&D Program of China grant (no. 2017YFA0105702).

Declaration of Interest: All authors declare that there are no conflicts of interest

Ethical Approval: All the animal experiments were approved approved in accordance with institution guidelines by the Ethics Committee of West China Hospital, Sichuan University. The tissue samples obtained from 50 glioma patients (age: from 55 to 75 years old; grade: WHO I-IV) were recruited to perform biopsy at West China hospital (Chengdu, China) and the study was approved by the Ethics Committee of West China Hospital.

Keywords: Glioma; SARI; MDSCs; SDF-1α; CXCR4

Suggested Citation

Zhang, Xin and Dai, Lei and Shi, Gang and Deng, Jie and Luo, Qiang and Xie, Qian and Cheng, Lin and Li, Chunlei and Lin, Yi and Wang, Qingnan and Liu, Yi and Fan, Ping and Zhang, Hantao and Su, Xiaolan and Zhang, Shuang and Yang, Yang and Hu, Xun and Gong, Qiyong and Yu, Dechao and Wei, Yuquan and Deng, Hongxin, SARI, a Novel Regulator of Glioma Microenvironment by Inhibiting CXCR4+ Myeloid-Derived Suppressor Cells Recruitment (May 16, 2019). Available at SSRN: https://ssrn.com/abstract=3391174 or http://dx.doi.org/10.2139/ssrn.3391174

Xin Zhang

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Southern Medical University - Nanfang Hospital

Guangzhou, Guangdong Province
China

Lei Dai

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Gang Shi

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Jie Deng

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Qiang Luo

Sichuan University - Department of Radiology

Sichuan
China

Qian Xie

Sichuan University - West China Hospital

No 37, Guoxue Road
Wuhou District
Chengdu, Sichuan Province 610041
China

Lin Cheng

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Chunlei Li

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Yi Lin

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Qingnan Wang

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Yi Liu

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Ping Fan

Sichuan University - West China Hospital

No 37, Guoxue Road
Wuhou District
Chengdu, Sichuan Province 610041
China

Hantao Zhang

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Xiaolan Su

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Shuang Zhang

Sichuan University - Cancer Center

Chengdu
China

Yang Yang

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Xun Hu

Sichuan University - West China Hospital

No 37, Guoxue Road
Wuhou District
Chengdu, Sichuan Province 610041
China

Qiyong Gong

Sichuan University - Huaxi MR Research Center (HMRRC)

China

Dechao Yu

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Yuquan Wei

Sichuan University - State Key Laboratory of Biotherapy

Chengdu
China

Sichuan University - Cancer Center

Chengdu
China

Sichuan University - National Collaborative Innovation Center for Biotherapy

Chengdu, Sichuan 610041
China

Hongxin Deng (Contact Author)

Sichuan University - State Key Laboratory of Biotherapy ( email )

Chengdu
China

Sichuan University - Cancer Center ( email )

Chengdu
China

Sichuan University - National Collaborative Innovation Center for Biotherapy ( email )

Chengdu, Sichuan 610041
China