IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46597-x.html
   My bibliography  Save this article

Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR

Author

Listed:
  • Cristiana Spinelli

    (The Research Institute of the McGill University Health Centre)

  • Lata Adnani

    (The Research Institute of the McGill University Health Centre)

  • Brian Meehan

    (The Research Institute of the McGill University Health Centre)

  • Laura Montermini

    (The Research Institute of the McGill University Health Centre)

  • Sidong Huang

    (McGill University
    McGill University)

  • Minjun Kim

    (McGill University)

  • Tamiko Nishimura

    (McGill University)

  • Sidney E. Croul

    (Dalhousie University)

  • Ichiro Nakano

    (Hokuto Social Medical Corporation, Hokuto Hospital)

  • Yasser Riazalhosseini

    (McGill University)

  • Janusz Rak

    (The Research Institute of the McGill University Health Centre
    McGill University
    McGill University)

Abstract

Targeting neovascularization in glioblastoma (GBM) is hampered by poor understanding of the underlying mechanisms and unclear linkages to tumour molecular landscapes. Here we report that different molecular subtypes of human glioma stem cells (GSC) trigger distinct endothelial responses involving either angiogenic or circumferential vascular growth (vasectasia). The latter process is selectively triggered by mesenchymal (but not proneural) GSCs and is mediated by a subset of extracellular vesicles (EVs) able to transfer EGFR/EGFRvIII transcript to endothelial cells. Inhibition of the expression and phosphorylation of EGFR in endothelial cells, either pharmacologically (Dacomitinib) or genetically (gene editing), abolishes their EV responses in vitro and disrupts vasectasia in vivo. Therapeutic inhibition of EGFR markedly extends anticancer effects of VEGF blockade in mice, coupled with abrogation of vasectasia and prolonged survival. Thus, vasectasia driven by intercellular transfer of oncogenic EGFR may represent a new therapeutic target in a subset of GBMs.

Suggested Citation

  • Cristiana Spinelli & Lata Adnani & Brian Meehan & Laura Montermini & Sidong Huang & Minjun Kim & Tamiko Nishimura & Sidney E. Croul & Ichiro Nakano & Yasser Riazalhosseini & Janusz Rak, 2024. "Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46597-x
    DOI: 10.1038/s41467-024-46597-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46597-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46597-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sheila K. Singh & Cynthia Hawkins & Ian D. Clarke & Jeremy A. Squire & Jane Bayani & Takuichiro Hide & R. Mark Henkelman & Michael D. Cusimano & Peter B. Dirks, 2004. "Identification of human brain tumour initiating cells," Nature, Nature, vol. 432(7015), pages 396-401, November.
    2. Charles P. Couturier & Shamini Ayyadhury & Phuong U. Le & Javad Nadaf & Jean Monlong & Gabriele Riva & Redouane Allache & Salma Baig & Xiaohua Yan & Mathieu Bourgey & Changseok Lee & Yu Chang David Wa, 2020. "Author Correction: Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    3. Charles P. Couturier & Shamini Ayyadhury & Phuong U. Le & Javad Nadaf & Jean Monlong & Gabriele Riva & Redouane Allache & Salma Baig & Xiaohua Yan & Mathieu Bourgey & Changseok Lee & Yu Chang David Wa, 2020. "Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    4. Alexandre F. Aissa & Abul B. M. M. K. Islam & Majd M. Ariss & Cammille C. Go & Alexandra E. Rader & Ryan D. Conrardy & Alexa M. Gajda & Carlota Rubio-Perez & Klara Valyi-Nagy & Mary Pasquinelli & Lawr, 2021. "Single-cell transcriptional changes associated with drug tolerance and response to combination therapies in cancer," Nature Communications, Nature, vol. 12(1), pages 1-25, December.
    5. Soniya Bastola & Marat S. Pavlyukov & Daisuke Yamashita & Sadashib Ghosh & Heejin Cho & Noritaka Kagaya & Zhuo Zhang & Mutsuko Minata & Yeri Lee & Hirokazu Sadahiro & Shinobu Yamaguchi & Svetlana Koma, 2020. "Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    6. Peter Carmeliet & Rakesh K. Jain, 2011. "Molecular mechanisms and clinical applications of angiogenesis," Nature, Nature, vol. 473(7347), pages 298-307, May.
    7. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabeth Ra, 2018. "Author Correction: A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 560(7716), pages 3-3, August.
    8. Erik Jung & Matthias Osswald & Miriam Ratliff & Helin Dogan & Ruifan Xie & Sophie Weil & Dirk C. Hoffmann & Felix T. Kurz & Tobias Kessler & Sabine Heiland & Andreas Deimling & Felix Sahm & Wolfgang W, 2021. "Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Claire Vinel & Gabriel Rosser & Loredana Guglielmi & Myrianni Constantinou & Nicola Pomella & Xinyu Zhang & James R. Boot & Tania A. Jones & Thomas O. Millner & Anaelle A. Dumas & Vardhman Rakyan & Je, 2021. "Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Susana I. Ramos & Zarmeen M. Mussa & Elisa N. Falk & Balagopal Pai & Bruno Giotti & Kimaada Allette & Peiwen Cai & Fumiko Dekio & Robert Sebra & Kristin G. Beaumont & Alexander M. Tsankov & Nadejda M., 2022. "An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Ziqi Gao & Chenran Jiang & Jiawen Zhang & Xiaosen Jiang & Lanqing Li & Peilin Zhao & Huanming Yang & Yong Huang & Jia Li, 2023. "Hierarchical graph learning for protein–protein interaction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Prach Techameena & Xiaona Feng & Kaiwen Zhang & Saida Hadjab, 2024. "The single-cell transcriptomic atlas iPain identifies senescence of nociceptors as a therapeutical target for chronic pain treatment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Akram A. Hamed & Daniel J. Kunz & Ibrahim El-Hamamy & Quang M. Trinh & Omar D. Subedar & Laura M. Richards & Warren Foltz & Garrett Bullivant & Matthaeus Ware & Maria C. Vladoiu & Jiao Zhang & Antony , 2022. "A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    7. Lata Adnani & Jordan Kassouf & Brian Meehan & Cristiana Spinelli & Nadim Tawil & Ichiro Nakano & Janusz Rak, 2022. "Angiocrine extracellular vesicles impose mesenchymal reprogramming upon proneural glioma stem cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Mykhaylo Slobodyanyuk & Alexander T. Bahcheli & Zoe P. Klein & Masroor Bayati & Lisa J. Strug & Jüri Reimand, 2024. "Directional integration and pathway enrichment analysis for multi-omics data," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Airi Jo-Watanabe & Toshiki Inaba & Takahiro Osada & Ryota Hashimoto & Tomohiro Nishizawa & Toshiaki Okuno & Sayoko Ihara & Kazushige Touhara & Nobutaka Hattori & Masatsugu Oh-Hora & Osamu Nureki & Tak, 2024. "Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Xinrui Zhou & Wan Yi Seow & Norbert Ha & Teh How Cheng & Lingfan Jiang & Jeeranan Boonruangkan & Jolene Jie Lin Goh & Shyam Prabhakar & Nigel Chou & Kok Hao Chen, 2024. "Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Balkrishna Chaube & Kathryn M. Citrin & Mahnaz Sahraei & Abhishek K. Singh & Diego Saenz Urturi & Wen Ding & Richard W. Pierce & Raaisa Raaisa & Rebecca Cardone & Richard Kibbey & Carlos Fernández-Her, 2023. "Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    12. Junyi Chen & Xiaoying Wang & Anjun Ma & Qi-En Wang & Bingqiang Liu & Lang Li & Dong Xu & Qin Ma, 2022. "Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Zongchao Sun & Likun Yang & Abdukahar Kiram & Jing Yang & Zhuangzhuang Yang & Liwei Xiao & Yujing Yin & Jing Liu & Yan Mao & Danxia Zhou & Hao Yu & Zheng Zhou & Dengqiu Xu & Yuhuan Jia & Chenyun Ding , 2023. "FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    16. Amy J. Gleichman & Riki Kawaguchi & Michael V. Sofroniew & S. Thomas Carmichael, 2023. "A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Yanming Ren & Zongyao Huang & Lingling Zhou & Peng Xiao & Junwei Song & Ping He & Chuanxing Xie & Ran Zhou & Menghan Li & Xiangqun Dong & Qing Mao & Chao You & Jianguo Xu & Yanhui Liu & Zhigang Lan & , 2023. "Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    18. Paweł Wańkowicz & Przemysław Nowacki & Bogusław Machaliński & Dorota Rogińska, 2019. "Biomarkers of Cancer Stem Cells in Glioblastoma Multiforme and Histological Picture of Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 23(3), pages 17365-17368, December.
    19. Umji Lee & Yadong Zhang & Yonglin Zhu & Allen Chilun Luo & Liyan Gong & Daniel M. Tremmel & Yunhye Kim & Victoria Sofia Villarreal & Xi Wang & Ruei-Zeng Lin & Miao Cui & Minglin Ma & Ke Yuan & Kai Wan, 2024. "Robust differentiation of human pluripotent stem cells into mural progenitor cells via transient activation of NKX3.1," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Franziska Haderk & Yu-Ting Chou & Lauren Cech & Celia Fernández-Méndez & Johnny Yu & Victor Olivas & Ismail M. Meraz & Dora Barbosa Rabago & D. Lucas Kerr & Carlos Gomez & David V. Allegakoen & Juan G, 2024. "Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46597-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.