Abstract
Glioblastoma is a highly aggressive malignant disease with notable resistance to chemotherapy. In this study, we found that leptin receptor (ObR)-positive glioblastoma cells were resistant to temozolomide (TMZ), and TMZ-resistant cells exhibited high expression of ObR. ObR can serve as a marker to enrich glioblastoma cells with some stem/progenitor cell traits, which explained the reason for TMZ resistance of ObR+ cells. STAT3-mediated SOX2/OCT4 signaling axis maintained the stem/progenitor cell properties of ObR+ cells, which indirectly regulated glioblastoma TMZ resistance. These findings gain insight into the molecular link between obesity and glioblastoma, and better understanding of this drug-resistant population may lead to the development of more effective therapeutic interventions for glioblastoma.
Keywords:
STAT3; chemoresistance; glioblastoma stem cells; leptin receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AC133 Antigen
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Antigens, CD / metabolism
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Antineoplastic Agents, Alkylating / pharmacology*
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Apoptosis / drug effects
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cell Line, Tumor / drug effects
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Dacarbazine / analogs & derivatives*
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Dacarbazine / pharmacology
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Drug Resistance, Neoplasm*
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Glioblastoma / metabolism
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Glioblastoma / pathology*
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Glycoproteins / metabolism
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Humans
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Octamer Transcription Factor-3 / metabolism
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Peptides / metabolism
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Receptors, Leptin / genetics*
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Receptors, Leptin / metabolism
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SOXB1 Transcription Factors / metabolism
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Temozolomide
Substances
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AC133 Antigen
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Antigens, CD
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Antineoplastic Agents, Alkylating
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Glycoproteins
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Octamer Transcription Factor-3
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POU5F1 protein, human
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Peptides
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Receptors, Leptin
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SOX2 protein, human
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SOXB1 Transcription Factors
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STAT3 Transcription Factor
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Dacarbazine
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Temozolomide