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Neural Precursor Cell-Derived Pleiotrophin Mediates Glioma Invasion of the Subventricular Zone

80 Pages Posted: 7 Apr 2018 Sneak Peek Status: Published

See all articles by Elizabeth Y. Qin

Elizabeth Y. Qin

Stanford University - Department of Neurology and Neurological Sciences

Dominique D. Cooper

Stanford University - Department of Neurology and Neurological Sciences

Keene L. Abbott

Stanford University - Baxter Laboratory in Stem Cell Biology; Stanford University - Department of Pathology

James Lennon

Stanford University - Department of Neurology and Neurological Sciences

Surya Nagaraja

Stanford University - Department of Neurology and Neurological Sciences

Alan Mackay

Institute of Cancer Research (ICR) - Division of Molecular Pathology; Institute of Cancer Research (ICR) - Division of Cancer Therapeutics

Chris Jones

Institute of Cancer Research (ICR) - Division of Molecular Pathology; Institute of Cancer Research (ICR) - Division of Cancer Therapeutics

Hannes Vogel

Stanford University - Department of Neurology and Neurological Sciences; Stanford University - Department of Pathology; Stanford University - Department of Neurosurgery; Stanford University - Department of Pediatrics

Peter K. Jackson

Stanford University - Baxter Laboratory in Stem Cell Biology; Stanford University - Department of Pathology

Michelle Monje

Stanford University - Department of Neurology and Neurological Sciences; Stanford University - Department of Pathology; Stanford University - Department of Neurosurgery; Stanford University - Department of Pediatrics

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Abstract

The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion.

Suggested Citation

Qin, Elizabeth Y. and Cooper, Dominique D. and Abbott, Keene L. and Lennon, James and Nagaraja, Surya and Mackay, Alan and Jones, Chris and Vogel, Hannes and Jackson, Peter K. and Monje, Michelle, Neural Precursor Cell-Derived Pleiotrophin Mediates Glioma Invasion of the Subventricular Zone (2018). Available at SSRN: https://ssrn.com/abstract=3155610 or http://dx.doi.org/10.2139/ssrn.3155610
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Elizabeth Y. Qin

Stanford University - Department of Neurology and Neurological Sciences

Room M016
Stanford, CA 94305
United States

Dominique D. Cooper

Stanford University - Department of Neurology and Neurological Sciences

Room M016
Stanford, CA 94305
United States

Keene L. Abbott

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

James Lennon

Stanford University - Department of Neurology and Neurological Sciences

Room M016
Stanford, CA 94305
United States

Surya Nagaraja

Stanford University - Department of Neurology and Neurological Sciences

Room M016
Stanford, CA 94305
United States

Alan Mackay

Institute of Cancer Research (ICR) - Division of Molecular Pathology

123 Old Brompton Road
London, England SW7 3RP
United Kingdom

Institute of Cancer Research (ICR) - Division of Cancer Therapeutics

123 Old Brompton Road
London, England SW7 3RP
United States

Chris Jones

Institute of Cancer Research (ICR) - Division of Molecular Pathology

123 Old Brompton Road
London, England SW7 3RP
United Kingdom

Institute of Cancer Research (ICR) - Division of Cancer Therapeutics

123 Old Brompton Road
London, England SW7 3RP
United States

Hannes Vogel

Stanford University - Department of Neurology and Neurological Sciences

Room M016
Stanford, CA 94305
United States

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Stanford University - Department of Neurosurgery

300 Pasteur Drive
Palo Alto, CA 94304
United States

Stanford University - Department of Pediatrics

291 Campus Drive
Li Ka Shing Learning and Knowledge Center
Stanford, CA 94305-5101
United States

Peter K. Jackson

Stanford University - Baxter Laboratory in Stem Cell Biology

Stanford, CA 94305
United States

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Michelle Monje (Contact Author)

Stanford University - Department of Neurology and Neurological Sciences ( email )

Room M016
Stanford, CA 94305
United States

Stanford University - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Stanford University - Department of Neurosurgery ( email )

300 Pasteur Drive
Palo Alto, CA 94304
United States

Stanford University - Department of Pediatrics ( email )

291 Campus Drive
Li Ka Shing Learning and Knowledge Center
Stanford, CA 94305-5101
United States

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