Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma

被引:29
|
作者
Wurm, Julian [1 ,2 ,3 ]
Behringer, Simon P. [1 ,2 ,3 ]
Ravi, Vidhya M. [1 ,2 ,3 ]
Joseph, Kevin [1 ,2 ,3 ]
Neidert, Nicolas [1 ,2 ,3 ]
Maier, Julian P. [1 ,2 ,3 ]
Doria-Medina, Roberto [2 ,3 ]
Follo, Marie [3 ,4 ]
Delev, Daniel [5 ]
Pfeifer, Dietmar [3 ,4 ]
Beck, Juergen [2 ,3 ]
Sankowski, Roman [3 ,6 ,7 ]
Schnell, Oliver [1 ,2 ,3 ]
Heiland, Dieter H. [1 ,2 ,3 ]
机构
[1] Univ Freiburg, Med Ctr, Translat NeuroOncol Res Grp, D-79106 Freiburg, Germany
[2] Univ Freiburg, Med Ctr, Dept Neurosurg, D-79106 Freiburg, Germany
[3] Freiburg Univ, Fac Med, D-79106 Freiburg, Germany
[4] Univ Freiburg, Med Ctr, Dept Med 1, D-79106 Freiburg, Germany
[5] Univ Aachen, Dept Neurosurg, D-79106 Aachen, Germany
[6] Univ Freiburg, Fac Med, Inst Neuropathol, D-79106 Freiburg, Germany
[7] Univ Freiburg, Fac Med, Berta Ottenstein Programme Clinician Scientists, D-79106 Freiburg, Germany
关键词
astrogliosis; glioblastoma microenvironment; CHI3L1; ASTROCYTES; EXPRESSION; PROLIFERATION; PROGENITOR; CHI3L1;
D O I
10.3390/cancers11101437
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex reveals a tumor-related up-regulation of Chitinase 3-like 1 (CHI3L1), a cytokine which is related to inflammation, extracellular tissue remodeling, and fibrosis. Further, we established and validated a co-culture model to investigate the impact of reactive astrocytes within the tumor microenvironment. Here we show that reactive astrocytes promote a subtype-shift of glioblastoma towards the mesenchymal phenotype, driving mitogen-activated protein kinases (MAPK) signaling as well as increased proliferation and migration. In addition, we demonstrate that MAPK signaling is directly caused by a CHI3L1-IL13RA2 co-binding, which leads to increased downstream MAPK and AKT signaling. This novel microenvironmental crosstalk highlights the crucial role of non-neoplastic cells in malignant brain tumors and opens up new perspectives for targeted therapies in glioblastoma.
引用
收藏
页数:13
相关论文
共 44 条
  • [31] Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9
    Low, Daren
    Subramaniam, Renuka
    Lin, Li
    Aomatsu, Tomoki
    Mizoguchi, Atsushi
    Ng, Aylwin
    DeGruttola, Arianna K.
    Lee, Chun Geun
    Elias, Jack A.
    Andoh, Akira
    Mino-Kenudson, Mari
    Mizoguchi, Emiko
    ONCOTARGET, 2015, 6 (34) : 36535 - 36550
  • [32] Isolation and Functional Characterization of Soybean BES1/BZR1 Homolog 3-Like 1 (GmBEH3L1) Associated with Dehydration Sensitivity and Brassinosteroid Signaling in Arabidopsis thaliana
    Park, Cho-Rong
    Van Tinh Nguyen
    Min, Ji-Hee
    Sang, Hyunkyu
    Lim, Gah-Hyun
    Kim, Cheol Soo
    PLANTS-BASEL, 2022, 11 (19):
  • [33] Chitinase 3 like-1 activates the Akt pathway, inducing NF-κB-dependent release of pro-inflammatory cytokines and promoting the proliferative ability in nasopharyngeal carcinoma cells
    Li, Dajun
    Fan, Gai
    Zhou, Yeqi
    CYTOKINE, 2024, 179
  • [34] Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-B) signaling during cell proliferation
    Thoompumkal, Indu Jose
    Rehna, Krishnan
    Anbarasu, Kumaraswamy
    Mahalingam, Sundarasamy
    CELL CYCLE, 2016, 15 (23) : 3251 - 3267
  • [35] Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells
    Areshkov, P. A.
    Kavsan, V. M.
    CYTOLOGY AND GENETICS, 2010, 44 (01) : 1 - 6
  • [36] TGF-β1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells
    Rodriguez-Garcia, Ana
    Samso, Paula
    Fontova, Pere
    Simon-Molas, Helga
    Manzano, Anna
    Castano, Esther
    Luis Rosa, Jose
    Martinez-Outshoorn, Ubaldo
    Ventura, Francesc
    Navarro-Sabate, Aurea
    Bartrons, Ramon
    FEBS JOURNAL, 2017, 284 (20) : 3437 - 3454
  • [37] Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1
    Lulli, Valentina
    Buccarelli, Mariachiara
    Ilari, Ramona
    Castellani, Giorgia
    De Dominicis, Chiara
    Di Giamberardino, Alessandra
    D'Alessandris, Quintino Giorgio
    Giannetti, Stefano
    Martini, Maurizio
    Stumpo, Vittorio
    Boe, Alessandra
    De Luca, Gabriele
    Biffoni, Mauro
    Marziali, Giovanna
    Pallini, Roberto
    Ricci-Vitiani, Lucia
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (10)
  • [38] Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells
    Zhang, Mingshi
    Liu, Jinrui
    Li, Mingjun
    Zhang, Shihua
    Lu, Yanmei
    Liang, Yanqiu
    Zhao, Kai
    Li, Yingfu
    EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2018, 16 (02) : 1477 - 1482
  • [39] The antidepressant-like effect of guanosine is dependent on GSK-3β inhibition and activation of MAPK/ERK and Nrf2/heme oxygenase-1 signaling pathways
    Rosa, Priscila B.
    Bettio, Luis E. B.
    Neis, Vivian B.
    Moretti, Morgana
    Werle, Isabel
    Leal, Rodrigo B.
    Rodrigues, Ana Lucia S.
    PURINERGIC SIGNALLING, 2019, 15 (04) : 491 - 504
  • [40] Neurotensin signaling regulates stem-like traits of glioblastoma stem cells through activation of IL-8/CXCR1/STAT3 pathway
    Zhou, Ji
    Yi, Liang
    Ouyang, Qing
    Xu, Lunshan
    Cui, Hongjuan
    Xu, Minhui
    CELLULAR SIGNALLING, 2014, 26 (12) : 2896 - 2902