Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas

Allison R. Pine; Stefano M. Cirigliano; James G. Nicholson; Yang Hu; Amanda Linkous; Ken Miyaguchi; Lincoln Edwards; Richa Singhania; Theodore H. Schwartz; Rohan Ramakrishna; David J. Pisapia; Matija Snuderl; Olivier Elemento; Howard A. Fine

doi:10.1158/2159-8290.cd-20-0057

journal article Jul 01, 2020

Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas

Allison R. Pine Stefano M. Cirigliano James G. Nicholson

Yang Hu

Amanda Linkous

Ken Miyaguchi Lincoln Edwards Richa Singhania Theodore H. Schwartz

Rohan Ramakrishna David J. Pisapia Matija Snuderl

Olivier Elemento

Howard A. Fine

Cancer Discovery Vol. 10 No. 7 pp. 964-979 · American Association for Cancer Research (AACR)

View at Publisher Save 10.1158/2159-8290.cd-20-0057

Abstract

Abstract

Glioblastoma (GBM), an incurable tumor, remains difficult to model and more importantly to treat due to its genetic/epigenetic heterogeneity and plasticity across cellular states. The ability of current tumor models to recapitulate the cellular states found in primary tumors remains unexplored. To address this issue, we compared single-cell RNA sequencing of tumor cells from 5 patients across four patient-specific glioblastoma stem cell (GSC)–derived model types, including glioma spheres, tumor organoids, glioblastoma cerebral organoids (GLICO), and patient-derived xenografts. We find that GSCs within the GLICO model are enriched for a neural progenitor–like cell subpopulation and recapitulate the cellular states and their plasticity found in the corresponding primary parental tumors. These data demonstrate how the contribution of a neuroanatomically accurate human microenvironment is critical and sufficient for recapitulating the cellular states found in human primary GBMs, a principle that may likely apply to other tumor models.

Significance:
It has been unclear how well different patient-derived GBM models are able to recreate the full heterogeneity of primary tumors. Here, we provide a complete transcriptomic characterization of the major model types. We show that the microenvironment is crucial for recapitulating GSC cellular states, highlighting the importance of tumor–host cell interactions.
See related commentary by Luo and Weiss, p. 907.
This article is highlighted in the In This Issue feature, p. 890

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Details

Published: Jul 01, 2020
Vol/Issue: 10(7)
Pages: 964-979

Authors

A

Allison R. Pine

1Caryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.; 2Tri-Institutional Program in Computational Biology and Medicine, New York, New York.

S

Stefano M. Cirigliano

3Department of Neurology, Weill Cornell Medicine, New York, New York.

J

James G. Nicholson

3Department of Neurology, Weill Cornell Medicine, New York, New York.

Y

Yang Hu

1Caryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.

A

Amanda Linkous

3Department of Neurology, Weill Cornell Medicine, New York, New York.

K

Ken Miyaguchi

3Department of Neurology, Weill Cornell Medicine, New York, New York.

L

Lincoln Edwards

4Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York.

R

Richa Singhania

3Department of Neurology, Weill Cornell Medicine, New York, New York.

T

Theodore H. Schwartz

5Department of Neurological Surgery, Weill Cornell Medicine, New York, New York.

R

Rohan Ramakrishna

5Department of Neurological Surgery, Weill Cornell Medicine, New York, New York.

D

David J. Pisapia

6Department of Pathology, Weill Cornell Medicine, New York, New York.

M

Matija Snuderl

7Department of Pathology, NYU Langone Medical Center, New York, New York.

O

Olivier Elemento

1Caryl and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York.

H

Howard A. Fine

3Department of Neurology, Weill Cornell Medicine, New York, New York.

Funding

NIH Award: 1DP1CA228040-01

Cite This Article

Allison R. Pine, Stefano M. Cirigliano, James G. Nicholson, et al. (2020). Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas. Cancer Discovery, 10(7), 964-979. https://doi.org/10.1158/2159-8290.cd-20-0057

Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas

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