Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma

Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Cancer, Metabolism, Stem Cells Articles Source Type: research

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Conditions:   Acute Myeloid Leukemia (AML);   Cancer Interventions:   Drug: Venetoclax;   Drug: Azacitidine;   Other: Best Supportive Care (BSC) Sponsor:   AbbVie Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionsOur findings suggest that exosomes derived from GEM-resistant pancreatic cancer stem cells mediate the horizontal transfer of drug-resistant traits to GEM-sensitive pancreatic cancer cells by delivering miR-210.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
In this report, we demonstrate potent anti‐myeloma effects of the TOPK inhibitor OTS514 for the fir st time. OTS514 induces cell cycle arrest and apoptosis at nanomolar concentrations in a series of human myeloma cell lines (HMCL) and prevents outgrowth of a putative CD138+ stem cell population from MM patient ‐derived peripheral blood mononuclear cells. In bone marrow cells from MM patients, OTS514 treatment exhibited preferential killing of the malignant CD138+ plasma cells compared with the CD138− compartment. In an aggressive mouse xenograft model, OTS964 given orally at 100  mg/kg 5 days per week w...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Ruiz Juan Antonio Marchal María Isabel Núñez Breast cancer is the most common cancer in women. Radiotherapy (RT) is one of the mainstay treatments for cancer but in some cases is not effective. Cancer stem cells (CSCs) within the tumor can be responsible for recurrence and metastasis after RT. Matrix metalloproteases (MMPs), regulated mainly by tissue inhibitors of metalloproteinases (TIMPs) and histone deacetylases (HDACs), may also contribute to tumor development by modifying its activity after RT. The aim of this work was to study the effects of RT on the expression of MMPs, TIMPs and HDACs ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensA greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. More than 80% of metastatic TGCT patients are cured with cisplatin-based chemotherapy. However, resistance can occur, which results in poor outcomes. The mechanisms of cisplatin hypersensitivity and resistance in these tumors and embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisp...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Publication date: Available online 9 November 2019Source: Stem Cell ResearchAuthor(s): Xiajun Li, Max Jiahua Li, Yang Yang, Yun BaiAbstractPluripotent stem cells are considered to be the ideal candidates for cell-based therapies in humans. In this regard, both nuclear transfer embryonic stem (ntES) cells and induced pluripotent stem (iPS) cells are particularly advantageous because patient-specific autologous ntES and iPS cells can avoid immunorejection and other side effects that may be present in the allogenic pluripotent stem cells derived from unrelated sources. However, they have been found to contain deleterious gene...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Abstract B-cell follicle represents a functionally dynamic microstructure within second lymphoid tissues, predominantly consisting of B cells, follicular T cells and DCs. Through intimate interactions with cognate B cells, follicular helper T cells (Tfh) initiate and facilitate germinal center (GC) reactions by providing signals required for producing high-affinity antibodies, as well as for the generation of long-lived antibody-secreting plasma cells and memory B cells. Concomitantly, germinal center reaction needs to be fine controlled to avoid autoimmunity or B-cell malignancies. Among immune cells residing in ...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
In conclusion, abrogation of PI3K/AKT signaling triggered by miR‑186‑5p/CXCL13 may contribute to ON pathogenesis. These results highlight the possible clinical value of miR‑186‑5p in treatment for non‑traumatic ON. PMID: 31702033 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Publication date: Available online 7 November 2019Source: Journal of BiotechnologyAuthor(s): Fahimeh Mollania, Nasser L. Hadipour, Nasrin MollaniaAbstractPyrimethamine is an effective drug in the cancer cell treatment and is a dihydrofolate reductase inhibitor. In this work, the amount of drug loading up on CNT and its cytotoxicity effect upon MCF-7 cell lines was surveyed. The novel applications of some drugs and nanocarriers can induce the differentiation of adipose mesenchymal cells into nerve cells. Hence carbon nanotube-pyrimethamine was used to differentiate mesenchymal stem cells into the neural category, for the fi...
Source: Journal of Biotechnology - Category: Biotechnology Source Type: research
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