"Hyaluronic acids mediate the infiltration, migration, and M2 polarization of macrophages: evaluating metabolic molecular phenotypes in gliomas"

作者全名："Zhang, Hao; Zhang, Nan; Dai, Ziyu; Wang, Zeyu; Zhang, Xun; Liang, Xisong; Zhang, Liyang; Feng, Songshan; Wu, Wantao; Ye, Weijie; Zhang, Jian; Luo, Peng; Liu, Zaoqu; Cheng, Quan; Liu, Zhixiong"

作者地址："[Zhang, Hao; Zhang, Nan; Dai, Ziyu; Wang, Zeyu; Zhang, Xun; Liang, Xisong; Zhang, Liyang; Feng, Songshan; Cheng, Quan; Liu, Zhixiong] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China; [Zhang, Hao; Zhang, Nan; Dai, Ziyu; Wang, Zeyu; Zhang, Xun; Liang, Xisong; Zhang, Liyang; Feng, Songshan; Wu, Wantao; Cheng, Quan; Liu, Zhixiong] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China; [Zhang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Zhang, Nan] Harbin Med Univ, Coll Bioinformat Sci & Technol, One Third Lab, Harbin, Peoples R China; [Wu, Wantao] Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Peoples R China; [Ye, Weijie; Cheng, Quan] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha, Peoples R China; [Zhang, Jian; Luo, Peng] Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China; [Liu, Zaoqu] Zhengzhou Univ, Affiliated Hosp 1, Dept Intervent Radiol, Zhengzhou, Peoples R China"

通信作者："Cheng, Q; Liu, ZX (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China."

来源：MOLECULAR ONCOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000865626100001

JCR分区：Q1

影响因子：6.6

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cell communication; gliomas; hyaluronic acid; macrophage; metabolism; tumor microenvironment

摘要："Gliomas cause high mortality around the world. The metabolic pattern of the tumor was previously suggested to be associated with the patient's survival outcome and immune activity. Yet, this relationship in glioma remains unknown. This study systematically evaluated the immune landscape in different phenotypes classified by metabolic-related pathways of 3068 glioma samples and 33 glioblastoma single-cell sequencing samples. Machine learning prediction analysis of microarray with R (pamr) was used for validating clustering results. A total of 5842 pan-cancer samples were used for external validation of the metabolic clusters. Cell Counting Kit-8 (CCK8) assay, cell clone assay, EdU assay, wound healing assay, Transwell assay, and co-culture assay were performed to verify the distinction in molecular characteristics among metabolic clusters. Metabolomics and RNA sequencing were performed on HS683 and U251 cells to annotate potential hyaluronic acid (HA)-mediated pathways. Three distinct metabolic phenotypes were identified. Metabolic cluster 1 correlated with a high number of immune infiltrating cells and poor survival of glioma patients. Metabolic clusters were proved with different levels of the macrophage markers CD68 and CD163 by multiplex immunofluorescence staining. Glioma cells from other metabolic clusters also expressed various levels of HA. HA was further found to mediate glioma proliferation, progression, and invasion. Moreover, HA potentially promoted macrophage recruitment and M2 polarization through the IL-1/CHI3L1 and TGF-b/CHI3L1 axes. HA also regulated the expression of PD-L1. This work revealed the significant connection between metabolic patterns, especially HA, and tumor immune infiltration in gliomas."

基金机构："National Natural Science Foundation of China [82172685, 82073893, 81703622, 81873635]; Hunan Provincial Natural Science Foundation of China [2022JJ20095, 2018SK2101, 2019JJ50963]; Hunan Provincial Health Committee Foundation of China [202204044869]; Xiangya Hospital Central South University Postdoctoral Foundation; Fundamental Research Funds for the Central Universities of Central South University; High Performance Computing Center of Central South University"

基金资助正文："This work was supported by the National Natural Science Foundation of China [Nos 82172685, 82073893, 81703622, 81873635]; Hunan Provincial Natural Science Foundation of China [Nos 2022JJ20095, 2018SK2101, 2019JJ50963]; Hunan Provincial Health Committee Foundation of China [202204044869]; Xiangya Hospital Central South University Postdoctoral Foundation; and Fundamental Research Funds for the Central Universities of Central South University. This work was supported in part by the High Performance Computing Center of Central South University."