دورية أكاديمية
أعرض في EDS

Repurposing Clemastine to Target Glioblastoma Cell Stemness.

التفاصيل البيبلوغرافية
العنوان: Repurposing Clemastine to Target Glioblastoma Cell Stemness.
المؤلفون: Sun MA; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.; Pathology Graduate Program, Duke University Medical Center, Durham, NC 27710, USA., Yang R; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Liu H; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.; Pathology Graduate Program, Duke University Medical Center, Durham, NC 27710, USA., Wang W; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Song X; The Ken & Ruth Davee Department of Neurology, Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Hu B; The Ken & Ruth Davee Department of Neurology, Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Reynolds N; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Roso K; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Chen LH; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Greer PK; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., Keir ST; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., McLendon RE; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., Cheng SY; The Ken & Ruth Davee Department of Neurology, Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Bigner DD; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., Ashley DM; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA., Pirozzi CJ; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA., He Y; The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
المصدر: Cancers [Cancers (Basel)] 2023 Sep 18; Vol. 15 (18). Date of Electronic Publication: 2023 Sep 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel)
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppressed the propagation of primary BTIC cultures bearing PDGFRA amplification. These effects on BTICs were accompanied by altered gene expression profiling indicative of their more differentiated states, resonating with the activity of clemastine in promoting the differentiation of normal oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes. Functional assays for pharmacological targets of clemastine revealed that the Emopamil Binding Protein (EBP), an enzyme in the cholesterol biosynthesis pathway, is essential for BTIC propagation and a target that mediates the suppressive effects of clemastine. Finally, we showed that a neural stem cell-derived mouse glioma model displaying predominantly proneural features was similarly susceptible to clemastine treatment. Collectively, these results identify pathways essential for maintaining the stemness and progenitor features of GBMs, uncover BTIC dependency on EBP, and suggest that non-oncology, low-toxicity drugs with OPC differentiation-promoting activity can be repurposed to target GBM stemness and aid in their treatment.
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معلومات مُعتمدة: NS101074 United States NS NINDS NIH HHS; R01 NS115403 United States NS NINDS NIH HHS; R01 NS101074 United States NS NINDS NIH HHS; P30 CA014236 United States CA NCI NIH HHS; R01 NS125318 United States NS NINDS NIH HHS; R21 NS126810 United States NS NINDS NIH HHS; CA014236 United States CA NCI NIH HHS; R21 NS122375 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Emopamil Binding Protein (EBP); clemastine; glioblastoma; stemness
تواريخ الأحداث: Date Created: 20230928 Latest Revision: 20231003
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10526458
DOI: 10.3390/cancers15184619
PMID: 37760589
قاعدة البيانات: MEDLINE
الوصف
تدمد:2072-6694
DOI:10.3390/cancers15184619