Inhibition of glioma progression by a newly discovered CD38 inhibitor

Eran Blacher; Bar Ben Baruch; Ayelet Levy; Nurit Geva; Keith D. Green; Sylvie Garneau-Tsodikova; Micha Fridman; Reuven Stein

doi:10.1002/ijc.29095

Bevacizumab/Radiation Halted High-Grade Glioma Progression

Clinical Neurology News ◽

10.1016/s1553-3212(07)70327-8 ◽

2007 ◽

Vol 3 (11) ◽

pp. 5

Author(s):

JANE SALODOF MACNEIL

Keyword(s):

High Grade Glioma ◽

High Grade ◽

Glioma Progression

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Faculty Opinions recommendation of Tumour-processed osteopontin and lactadherin drive the protumorigenic reprogramming of microglia and glioma progression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726264227.793516841 ◽

2016 ◽

Author(s):

Rachel Buchsbaum

Keyword(s):

Glioma Progression

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Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-Catenin: Association with Human Glioma Progression

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527313666141023121550 ◽

2014 ◽

Vol 13 (8) ◽

pp. 1413-1426 ◽

Cited By ~ 13

Author(s):

Hanuma Karnati ◽

Manas Panigrahi ◽

Noor Shaik ◽

Nigel Greig ◽

S. Bagadi ◽

...

Keyword(s):

Human Glioma ◽

Regulated Expression ◽

Glioma Progression

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LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2

Cell Death and Differentiation ◽

10.1038/s41418-020-0558-4 ◽

2020 ◽

Vol 27 (11) ◽

pp. 3021-3036 ◽

Cited By ~ 2

Author(s):

Hua Yu ◽

Jun Ding ◽

Hongwen Zhu ◽

Yao Jing ◽

Hu Zhou ◽

...

Keyword(s):

Molecular Chaperone ◽

Glioma Cell ◽

Lysyl Oxidase ◽

The Cancer Genome Atlas ◽

Loss Of Function ◽

Protein Levels ◽

Important Mediator ◽

Cancer Genome Atlas ◽

Potential Strategy ◽

Glioma Progression

Abstract The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical significance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. LOXL1 was found to exhibit antiapoptotic activity by interacting with multiple antiapoptosis modulators, especially BAG family molecular chaperone regulator 2 (BAG2). LOXL1-D515 interacted with BAG2-K186 through a hydrogen bond, and its lysyl oxidase activity prevented BAG2 degradation by competing with K186 ubiquitylation. Then, we discovered that LOXL1 expression was specifically upregulated through the VEGFR-Src-CEBPA axis. Clinically, the patients with higher LOXL1 levels in their blood had much more abundant BAG2 protein levels in glioma tissues. Conclusively, LOXL1 functions as an important mediator that increases the antiapoptotic capacity of tumor cells, and approaches targeting LOXL1 represent a potential strategy for treating glioma. In addition, blood LOXL1 levels can be used as a biomarker to monitor glioma progression.

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Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

Cell Death and Disease ◽

10.1038/s41419-021-03664-1 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jianye Xu ◽

Jian Zhang ◽

Zongpu Zhang ◽

Zijie Gao ◽

Yanhua Qi ◽

...

Keyword(s):

Macrophage Polarization ◽

Autophagy Induction ◽

Antitumor Immunotherapy ◽

Novel Biomarkers ◽

And Migration ◽

Immunosuppressive Microenvironment ◽

Proliferation And Migration ◽

Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

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