Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy

Soniya Bastola, Marat S. Pavlyukov, Daisuke Yamashita, Sadashib Ghosh, Heejin Cho, Noritaka Kagaya, Zhuo Zhang, Mutsuko Minata, Yeri Lee, Hirokazu Sadahiro, Shinobu Yamaguchi, Svetlana Komarova, Eddy Yang, James Markert, Louis B. Nabors, Krishna Bhat, James Lee, Qin Chen, David K. Crossman, Kazuo Shin-Ya, Do-Hyun Nam and Ichiro Nakano ()
Additional contact information
Soniya Bastola: University of Alabama at Birmingham
Marat S. Pavlyukov: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Daisuke Yamashita: University of Alabama at Birmingham
Sadashib Ghosh: University of Alabama at Birmingham
Heejin Cho: Research Institute for Future Medicine
Noritaka Kagaya: National Institute of Advanced Industrial Science and Technology
Zhuo Zhang: University of Alabama at Birmingham
Mutsuko Minata: University of Alabama at Birmingham
Yeri Lee: Research Institute for Future Medicine
Hirokazu Sadahiro: Yamaguchi University
Shinobu Yamaguchi: University of Alabama at Birmingham
Svetlana Komarova: University of Alabama at Birmingham
Eddy Yang: University of Alabama at Birmingham
James Markert: University of Alabama at Birmingham
Louis B. Nabors: University of Alabama at Birmingham
Krishna Bhat: The University of Texas, M.D. Anderson Cancer Center
James Lee: Ohio State University
Qin Chen: University of Alabama at Birmingham
David K. Crossman: University of Alabama at Birmingham
Kazuo Shin-Ya: National Institute of Advanced Industrial Science and Technology
Do-Hyun Nam: Samsung Medical Center, Sungkyunkwan University School of Medicine
Ichiro Nakano: University of Alabama at Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Intratumor spatial heterogeneity facilitates therapeutic resistance in glioblastoma (GBM). Nonetheless, understanding of GBM heterogeneity is largely limited to the surgically resectable tumor core lesion while the seeds for recurrence reside in the unresectable tumor edge. In this study, stratification of GBM to core and edge demonstrates clinically relevant surgical sequelae. We establish regionally derived models of GBM edge and core that retain their spatial identity in a cell autonomous manner. Upon xenotransplantation, edge-derived cells show a higher capacity for infiltrative growth, while core cells demonstrate core lesions with greater therapy resistance. Investigation of intercellular signaling between these two tumor populations uncovers the paracrine crosstalk from tumor core that promotes malignancy and therapy resistance of edge cells. These phenotypic alterations are initiated by HDAC1 in GBM core cells which subsequently affect edge cells by secreting the soluble form of CD109 protein. Our data reveal the role of intracellular communication between regionally different populations of GBM cells in tumor recurrence.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18189-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18189-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18189-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().