Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes

Joshua D Frenster; Michael Kader; Scott Kamen; James Sun; Luis Chiriboga; Jonathan Serrano; Devin Bready; Danielle Golub; Niklas Ravn-Boess; Gabriele Stephan; Andrew S Chi; Sylvia C Kurz; Rajan Jain; Christopher Y Park; David Fenyo; Ines Liebscher; Torsten Schöneberg; Giselle Wiggin; Robert Newman; Matt Barnes; John K Dickson; Douglas J MacNeil; Xinyan Huang; Nadim Shohdy; Matija Snuderl; David Zagzag; Dimitris G Placantonakis

doi:10.1093/noajnl/vdaa053

Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes

Neurooncol Adv. 2020 Apr 28;2(1):vdaa053. doi: 10.1093/noajnl/vdaa053. eCollection 2020 Jan-Dec.

Authors

Joshua D Frenster^{1

2}, Michael Kader¹, Scott Kamen³, James Sun¹, Luis Chiriboga^{3

4}, Jonathan Serrano³, Devin Bready¹, Danielle Golub¹, Niklas Ravn-Boess¹, Gabriele Stephan¹, Andrew S Chi^{5

4

6}, Sylvia C Kurz^{5

4

6}, Rajan Jain^{7

4

6}, Christopher Y Park³, David Fenyo^{8

9}, Ines Liebscher¹⁰, Torsten Schöneberg¹⁰, Giselle Wiggin¹¹, Robert Newman¹¹, Matt Barnes¹¹, John K Dickson¹², Douglas J MacNeil¹³, Xinyan Huang¹³, Nadim Shohdy¹³, Matija Snuderl^{3

4

6}, David Zagzag^{1

3

4

6}, Dimitris G Placantonakis^{1

2

4

6

14}

Affiliations

¹ Departments of Neurosurgery, New York, New York, USA.
² NYU Grossman School of Medicine, New York, New York, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, New York, USA.
³ Pathology, New York, New York, USA.
⁴ Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, New York, USA.
⁵ Neurology, New York, New York, USA.
⁶ Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, New York, USA.
⁷ Radiology, New York, New York, USA.
⁸ Biochemistry and Molecular Pharmacology, New York, New York, USA.
⁹ Institute for Systems Genetics, NYU Grossman School of Medicine, New York, New York, USA.
¹⁰ Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.
¹¹ Heptares Therapeutics Ltd, Cambridge, UK.
¹² AptaChem Consulting LLC, Apex, North Carolina, USA.
¹³ Office for Therapeutic Alliances, NYU Grossman School of Medicine, New York, New York, USA.
¹⁴ Neuroscience Institute, NYU Grossman School of Medicine, New York, New York, USA.

Abstract

Background: Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown.

Methods: We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas.

Results: We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors.

Conclusion: The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.

Keywords: G protein-coupled receptor; GPR133; adhesion; glioblastoma; glioma.

Abstract

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