Frontiers in Oncology (Sep 2022)
GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide
- Sweta Parik,
- Sweta Parik,
- Sweta Parik,
- Sweta Parik,
- Juan Fernández-García,
- Juan Fernández-García,
- Francesca Lodi,
- Francesca Lodi,
- Karen De Vlaminck,
- Karen De Vlaminck,
- Marleen Derweduwe,
- Steven De Vleeschouwer,
- Raf Sciot,
- Wietse Geens,
- Linqian Weng,
- Francesca Maria Bosisio,
- Francesca Maria Bosisio,
- Gabriele Bergers,
- Gabriele Bergers,
- Johnny Duerinck,
- Frederick De Smet,
- Diether Lambrechts,
- Diether Lambrechts,
- Jo A. Van Ginderachter,
- Jo A. Van Ginderachter,
- Sarah-Maria Fendt,
- Sarah-Maria Fendt
Affiliations
- Sweta Parik
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Sweta Parik
- Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
- Sweta Parik
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Sweta Parik
- Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium
- Juan Fernández-García
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Juan Fernández-García
- Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
- Francesca Lodi
- Laboratory for Translational Genetics, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Francesca Lodi
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
- Karen De Vlaminck
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Karen De Vlaminck
- Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium
- Marleen Derweduwe
- Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium
- Steven De Vleeschouwer
- Department of Neurosurgery, University Hospital Leuven, Leuven, Belgium
- Raf Sciot
- Department of Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium
- Wietse Geens
- 0Department of Neurosurgery, UZ Brussel, Jette, Belgium
- Linqian Weng
- 1Laboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Francesca Maria Bosisio
- Department of Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium
- Francesca Maria Bosisio
- 2Laboratory of Translational Cell & Tissue Research Department of Pathology, University Hospital Leuven, Leuven, Belgium
- Gabriele Bergers
- 1Laboratory of Tumor Microenvironment and Therapeutic Resistance, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Gabriele Bergers
- 3Department of Neurological Surgery, UCSF Comprehensive Cancer Center, University of California San Francisco (UCSF), San Francisco, CA, United States
- Johnny Duerinck
- 0Department of Neurosurgery, UZ Brussel, Jette, Belgium
- Frederick De Smet
- Laboratory for Precision Cancer Medicine, Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven, Belgium
- Diether Lambrechts
- Laboratory for Translational Genetics, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
- Jo A. Van Ginderachter
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Jo A. Van Ginderachter
- Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, Brussels, Belgium
- Sarah-Maria Fendt
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium
- Sarah-Maria Fendt
- Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Leuven, Belgium
- DOI
- https://doi.org/10.3389/fonc.2022.988872
- Journal volume & issue
-
Vol. 12
Abstract
Glioblastoma is a highly lethal grade of astrocytoma with very low median survival. Despite extensive efforts, there is still a lack of alternatives that might improve these prospects. We uncovered that the chemotherapeutic agent temozolomide impinges on fatty acid synthesis and desaturation in newly diagnosed glioblastoma. This response is, however, blunted in recurring glioblastoma from the same patient. Further, we describe that disrupting cellular fatty acid homeostasis in favor of accumulation of saturated fatty acids such as palmitate synergizes with temozolomide treatment. Pharmacological inhibition of SCD and/or FADS2 allows palmitate accumulation and thus greatly augments temozolomide efficacy. This effect was independent of common GBM prognostic factors and was effective against cancer cells from recurring glioblastoma. In summary, we provide evidence that intracellular accumulation of saturated fatty acids in conjunction with temozolomide based chemotherapy induces death in glioblastoma cells derived from patients.
Keywords
