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Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism.
Zhao, Linjie; Qiu, Zhixin; Yang, Zhengnan; Xu, Lian; Pearce, Thomas M; Wu, Qiulian; Yang, Kailin; Li, FuLong; Saulnier, Olivier; Fei, Fan; Yu, Huaxu; Gimple, Ryan C; Varadharajan, Venkateshwari; Liu, Juxiu; Hendrikse, Liam D; Fong, Vernon; Wang, Wei; Zhang, Jiao; Lv, Deguan; Lee, Derrick; Lehrich, Brandon M; Jin, Chunyu; Ouyang, Liang; Dixit, Deobrat; Wu, Haoxing; Wang, Xiang; Sloan, Andrew E; Wang, Xiuxing; Huan, Tao; Mark Brown, J; Goldman, Steven A; Taylor, Michael D; Zhou, Shengtao; Rich, Jeremy N.
Afiliação
  • Zhao L; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Qiu Z; Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Yang Z; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Xu L; Department of Anesthesiology, Zhongshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
  • Pearce TM; Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, and Collaborative Innovation Center, Chengdu, China.
  • Wu Q; Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, China.
  • Yang K; Department of Pathology, Division of Neuropathology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Li F; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Saulnier O; Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
  • Fei F; Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
  • Yu H; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Gimple RC; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Varadharajan V; Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
  • Liu J; Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
  • Hendrikse LD; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • Fong V; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA.
  • Wang W; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Zhang J; Division of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
  • Lv D; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Lee D; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Lehrich BM; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Jin C; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Ouyang L; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dixit D; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Wu H; Department of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, China.
  • Wang X; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Sloan AE; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Wang X; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Huan T; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Mark Brown J; University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA.
  • Goldman SA; Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Taylor MD; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu, China.
  • Zhou S; Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • Rich JN; Huaxi MR Research Center, Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Nat Cancer ; 5(1): 147-166, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38172338
ABSTRACT
Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1K273 acetylation in glioblastoma specimens, informing patient outcome. Collectively, glioblastomas contain previously unrecognized LECs that promote the molecular crosstalk between endothelial and tumor cells, offering potentially alternative therapeutic strategies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma Limite: Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos