HMMR maintains the stemness and tumorigenicity of glioblastoma stem-like cells.
Glioblastoma (GBM) stem cells (GSC) are a subpopulation of tumor cells that display stem-like characteristics (stemness) and play unique roles in tumor propagation, therapeutic resistance, and tumor recurrence. Therapeutic targets in GSCs are a focus of increasing interest to improve GBM therapy. Here we report that the hyaluronan-mediated motility receptor (HMMR) is highly expressed in GBM tumors, where it supports the self-renewal and tumorigenic potential of GSCs. HMMR silencing impairs GSC self-renewal and inhibits the expression of GSC markers and regulators. Furthermore, HMMR silencing suppresses GSC-derived tumor growth and extends the survival of mice bearing GSC xenografts. Conversely, HMMR overexpression promotes GSC self-renewal and intracranial tumor propagation. In human GBM tumor specimens, HMMR expression is correlated positively with the expression of stemness-associated markers and regulators. Our findings identify HMMR as a candidate therapeutic target to GSCs as a GBM treatment strategy.
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Jessica
J
Tilghman
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Hao
H
Wu
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Yingying
Y
Sang
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Xiaohai
X
Shi
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Hugo
H
Guerrero-Cazares
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Alfredo
A
Quinones-Hinojosa
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Charles G
CG
Eberhart
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia ying@kennedykrieger.org laterra@kennedykrieger.org.
John
J
Laterra
Authors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GeorgiaAuthors' Affiliations: Hugo W. Moser Research Institute at Kennedy Krieger; Departments of Neurology, Neuroscience, Oncology, Neurosurgery, and Pathology, Johns Hopkins School of Medicine; Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia ying@kennedykrieger.org laterra@kennedykrieger.org.
Mingyao
M
Ying
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*
D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor