The secreted glycolytic enzyme GPI/AMF stimulates glioblastoma cell migration and invasion in an autocrine fashion but can have anti-proliferative effects

Kathagen-Buhmann, Annegret; Maire, Cécile L.; Weller, Jonathan; Schulte, Alexander; Matschke, Jakob; Holz, Mareike; Ligon, Keith L.; Glatzel, Markus; Westphal, Manfred; Lamszus, Katrin

doi:10.1093/neuonc/noy117

Cited by 24 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For cell migration and invasion analysis, the metastatic melanoma SK-MEL-24 cells were subjected to treatment with 0, 12.5, 25, and 50 μM concentrations of ursolic acid. The cell migration and invasion assays were then performed as described previously [14].…”

Section: Methodsmentioning

confidence: 99%

Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

Liu

Du²,

2019

Med Sci Monit

View full text Add to dashboard Cite

Background Ursolic acid is an important bioactive triterpenoid that has been reported to be of tremendous pharmacological importance. However, the anticancer potential of ursolic acid has not been examined against metastatic melanoma cells. Therefore, in this study we examined the anticancer potential of ursolic acid and its mode of action. Material/Methods WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by AO/EB staining using fluorescence microscopy. Cell migration and invasion were assessed by Boyden chamber assay. Protein expression was checked by Western blotting. Results The results revealed that ursolic acid exerts significant (p<0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC 50 of ursolic acid against SK-MEL-24 cells was 25 μM. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of Bcl-2. Ursolic acid also halted the SK-MEL-24 cells at G0/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p<0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK. Conclusions Ursolic acid appears to be a potent molecule for the treatment of melanoma.

show abstract

Section: Methodsmentioning

confidence: 99%

Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

Liu

Du²,

2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…The metabolic trend of glioma cells switches between glycolysis and PPP according to the concentration of oxygen. Under hypoxia, glioma cells overexpressed glycolytic enzymes to maintain energy supply and promote migration, while up-regulating PPP enzymes for rapid proliferation and division under oxygen-rich condition ( Kathagen-Buhmann et al, 2016 ; Kathagen-Buhmann et al, 2018 ). Glycolysis was highly activated in HGG cells with invasiveness and resistance to conventional treatment ( Corbin et al, 2017 ), but weaker glycolysis was detected in LGG cells with IDH1 mutations, which restricted their energy and made them less aggressive ( Fack et al, 2017 ).…”

Section: Metabolic Properties Of Glioma Cellsmentioning

confidence: 99%

“…The metabolic reprogramming allowed glioma cells to proliferate regardless of the ischemic lesion ( Table 1 ), and endowed them with strong migration capabilities for a better growth condition ( Kathagen-Buhmann et al, 2018 ), enabling the rapid invasion into healthy brain tissues. Concurrently, to cope with changes in nutritional sources, the metabolic plasticity of glioma cells resulted in the resistance to anti-metabolic therapies, including diet and drugs ( De Feyter et al, 2016 ; Shibao et al, 2018 ).…”

Section: Metabolic Properties Of Glioma Cellsmentioning

confidence: 99%

Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

Qiu

Zhong

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.

show abstract

“…At the same time, SRGN promotes the activation of Ras-related C3 botulinum toxin substrate 1 (RAC1) and cell division control protein 42 homolog (CDC42) to enhance cytoskeletal reorganization, eventually enhancing the migratory ability of cancer cells ( 23 ). Other secretory proteins promoting tumor cell invasion and migration include Galectin-8 secreted from GBM ( 24 ), glucose-6-phosphate isomerase (GPI) secreted from glioma cells ( 25 ), and IL-1β secreted from pancreatic cancer cells with high CD133 expression ( 26 ).…”

Section: Secretory Proteins Mediate Regulation Between Tumor Cellsmentioning

confidence: 99%

Research advances of secretory proteins in malignant tumors

Zhang¹,

Hao²,

Cai³

et al. 2021

Chinese Journal of Cancer Research

View full text Add to dashboard Cite

show abstract

The secreted glycolytic enzyme GPI/AMF stimulates glioblastoma cell migration and invasion in an autocrine fashion but can have anti-proliferative effects

Cited by 24 publications

References 29 publications

Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway

Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

Research advances of secretory proteins in malignant tumors

Contact Info

Product

Resources

About