Hyperglycemia promotes an aggressive phenotype in breast cancer cells
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ABSTRACT:
PROVIDER: PRJNA561818 | ENA |
REPOSITORIES: ENA
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Project description:Diabetes and breast cancer are common diseases with a major impact on the health sector in Mexico and worldwide. Epidemiological and experimental works support the link between type 2 diabetes and breast cancer; these data support that insulin resistance, hyperglycemia, hyperinsulinemia, and elevated levels of IGF-1 in patients with type II diabetes mellitus promote growth and invasiveness of tumor cells. The aim of the present work was to determine, by microarray, the mechanisms of action and signaling of a hyperglycemic microenvironment in the cell line (MDA-MB-231) and its effect to treatment with cisplatin (CCP). MDA-MB-231 breast cancer cells were cultured in DMEM medium, supplemented with 10% fetal bovine serum and antibiotics at 5% CO2, at 37 ˚C. We proceeded to extract total RNA for the analysis of microarrays under LG (low glucose) and HG (high glucose) conditions; for the cDNA synthesis, it was labeled with dUTP-Cy3 or dUTP-Cy5 fluorophores, using a CyScribe Firs-Strand cDNA kit. The analysis was carried out through the KEGG pathways program; some bioenergetic metabolism processes (glycolysis, biosynthesis of purines and pyrimidines, and metabolism of glycerol phospholipids) were found altered, which fulfill the feedback function to the cellular microenvironment, activating some signaling processes, such as the Hippo route, PI3K-Akt, Jak-STAT, MAPK, Ras, Wnt/β-catenin, apoptosis, and favoring an aggressive phenotype and drug resistance in a hyperglycemic microenvironment. The microarray analysis was validated by qRT-PCr of the tetraspanin and Frizzled genes.
2019-08-24 | GSE136277 | GEO
Project description:SP8 promotes an aggressive phenotype in hepatoblastoma via FGF8 activation
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Project description:As miR-210 expression is correlated to poor prognosis both in estrogen-positive and in estrogen-negative breast cancer (BC) patients, we aimed to investigate the biological processes regulated by miR-210 and which may elucidate its function in the aggressive phenotype of high grade breast cancer. We performed in silico functional analyses of the genes deregulated upon miR-210 overexpression in MCF7 BC cell line and upon miR-210 repression in MDA-MB-231 BC cell line using lentiviral transduction. Gene expression profiling analysis of these cells revealed the deregulation of genes involved in several biological pathways including cell adhesion, extracellular structure organization, epithelial cell proliferation, cell division, cell cycle and immune response. MCF-7 cells overexpressing miR-210 (or control) and MDA-MB-231 cells in which miR-210 (or control) is repressed were used for RNA extraction and hybridization on Affymetrix microarrays.
2011-07-01 | E-GEOD-25162 | biostudies-arrayexpress
Project description:We report that EVs originated from cancer cells can modulate glucose metabolism in the recipient cancer cells and induce cell proliferation and aggressive phenotype. Two breast cancer cell lines with different levels of glycolytic activity, MDA-MB-231 of a claudin low-type breast cancer cell and MCF7 of luminal type breast cancer cell, were selected and co-cultured, as the originating and recipient cells using indirect co-culture system such as transwell system or microfluidic system. Proteomic profiling of the co-cultured MCF7 cells revealed proliferation and dedifferentiation of the MCF7 cells following co-culture with the MDA-MB-231 cells. Transcriptomic analysis demonstrated that glycolysis increased in the co-cultured MCF7 cells, and the component analysis of glycolysis-related genes revealed that the second-most component after cytoplasm was extracellular exosomes. In addition, 36 significant KEGG pathways were identified in a total of 856 proteins identified by proteomin analysis of MDA-MB-231-induced EVs. Among these pathways were the main pathways (glycolysis/gluconeogenesis, pyruvate metabolism, and PI3K-Akt signaling pathways) that could explain the metabolic modulation of MCF7 cells. In our work, we indirectly show that it is MDA-MB-231-derived EVs that play an important role in this phenomenon. Our study highlights the potential effects of aggressive cancer cells on other surrounding cancer cells through EVs.
2021-09-09 | GSE183551 | GEO
Project description:As miR-210 expression is correlated to poor prognosis both in estrogen-positive and in estrogen-negative breast cancer (BC) patients, we aimed to investigate the biological processes regulated by miR-210 and which may elucidate its function in the aggressive phenotype of high grade breast cancer. We performed in silico functional analyses of the genes deregulated upon miR-210 overexpression in MCF7 BC cell line and upon miR-210 repression in MDA-MB-231 BC cell line using lentiviral transduction. Gene expression profiling analysis of these cells revealed the deregulation of genes involved in several biological pathways including cell adhesion, extracellular structure organization, epithelial cell proliferation, cell division, cell cycle and immune response.
2011-07-01 | GSE25162 | GEO
Project description:Diabetic foot ulcers (DFUs) are characterized by a chronic inflammation state which prevents cutaneous wound healing, andDFUs eventually lead to infection and leg amputation. Macrophages located in DFUs are locked in an pro-inflammatory phenotype. In this study, the effect of hyperglycemia and hypoxia on the macrophage phenotype was analyzed. For this purpose, a microarray was performed to study the gene expression profile of macrophages cultivated in a high glucose concentration. Hyperglycemia upregulated the expression of pro-inflammatory cytokines such as TNF-α, IL-1, IL-6, chemokines and downregulatd the expression of two receptors involved in phagocytosis (CD 36 and Class B scavenger type I receptors). In addition, eleven anti-apoptotic factors were upregulated whereas three pro-apoptotic ones were downregulated. Subsequently, the contribution of hypoxia and hyperglycemia to chronic inflammation and their potential synergic effect was evaluated on activated THP-1 derived macrophages. A long term post activation effect (17 hours) was only observed on the upregulation of pro-inflammatory cytokines when hypoxia was combined with a high glucose concentration. In contrast, hyperglycemia and hypoxia did not have any effect on wound healing molecules such as TGF-β1. Taken together, the results show that hyperglycemia acts in synergy with hypoxia to maintain a chronic inflammation state in macrophages.
2019-07-24 | GSE132187 | GEO
Project description:Elevated ETV6 expression in glioma promotes an aggressive in vitro phenotype associated with shorter patient survival
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Project description:Diabetes is associated with a more aggressive form of atherosclerosis. Thrombospondin-1 (TSP-1), an extracellular matrix protein, is an acute phase reactant that induces vascular smooth muscle (VSMC) migration and proliferation in areas of vascular injury, and is also upregulated in VSMCs exposed to hyperglycemia. We hypothesized that hyperglycemia amplifies the expression of genes induced by TSP-1 in VSMCs. Human aortic VSMCs were cultured in DMEM supplemented with 10 % FBS and 1% antibiotics, cells were used between passages three and five. VSMCs were preincubated in DMEM containing 0.2% FBS with 5 mM glucose (normoglycemia), 25 mM glucose (hyperglycemia), 25 mM mannose (osmotic control), TSP-1 (20µg/mL), 25 mM glucose + TSP-1 (20µg/mL) or 25 mM mannose + TSP-1 (20µg/mL). Data analysis revealed that TSP-1 stimulates gene expression relevant to the pathogenesis of atherosclerosis and diabetic vascular disease. Total RNA was extracted from replicate cultures of human aortic VSMCs and microarray analysis performed for a total of 18 samples (3 replicates per condition) using the Human Gene Array ST.
2009-08-11 | E-GEOD-17556 | biostudies-arrayexpress
Project description:Melanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness; however, the underlying molecular details are elusive. The mitochondrial calcium uniporter (MCU) complex is a major route for calcium into the mitochondrial matrix but if and how MCU affects melanoma pathobiology is not understood. Here, we show that MCUA expression correlates with melanoma patient survival, similarly as in kidney, cervical and other cancers, while in pancreatic, breast and liver cancer, this correlation is inverse. Knockdown (KD) of MCUA suppressed melanoma cell growth but promoted migration and invasion in 2D and 3D cultures. In melanoma xenografts, MCUA_KD reduced tumor volumes but promoted lung metastases. Proteomic analyses and protein microarrays identified pathways that link MCUA abundance and melanoma cell phenotype and suggested a major role for metabolic and redox regulation. Accordingly, antioxidants enhanced melanoma cell migration, while pro-oxidants diminished the MCUA_KD-induced invasive phenotype. Furthermore, MCUA_KD amplified the resistance of melanoma cells to immunotherapies and ferroptosis. Col¬lectively, we demonstrate that MCUA controls melanoma aggressive behavior and therapeutic sen¬sitivity. Manipulations of mitochondrial calcium and redox homeostasis, in combination with cur¬rent therapies, should be considered in treating advanced melanoma.
2022-10-30 | PXD029132 | Pride