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-YaDo Hyun Nam, Ichiro Nakano

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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.

Original languageEnglish
Article number4660
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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