GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors

Ryniawec, John M.; Coope, Matthew R.; Loertscher, Emily; Bageerathan, Vignesh; Pessôa, Diogo de Oliveira; Warfel, Noel A.; Cress, Anne E.; Padi, Megha; Rogers, Gerald S.

doi:10.3390/diagnostics12030676

Cited by 8 publications

(9 citation statements)

References 74 publications

(103 reference statements)

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“…Hypoxia is a common feature in the TME because the uncontrolled proliferation of tumor cells mismatches the relatively insufficient supply of blood as well as oxygen, leading to stress-tolerant tumor cell survival [ 38 ]. In hypoxic-cultured prostate cell lines and hypoxic regions of xenograft tumors, the expression of SLC2A3 was significantly increased [ 39 ]. Combining previous results with our present study, we speculate that SLC2A3 predicting unfavorable prognosis in HNSCC could associate with glucose metabolism and HIF-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Chu¹,

Zheng

Li³

et al. 2022

Analytical Cellular Pathology

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Background. SLC2A3 is upregulated in various cancer types and promotes proliferation, invasion, and metabolism. However, its role in the prognosis and immune regulation of head and neck squamous cell carcinoma (HNSCC) is still obscure. This study is aimed at exploring the prognostic and immunotherapeutic potential of SLC2A3 in HNSCC. Methods. All data were downloaded from TCGA database and integrated via R software. SLC2A3 expression was evaluated using R software, TIMER, CPTAC, and HPA databases. The association between SLC2A3 expression and clinicopathologic characteristics was assessed by R software. The effect of SLC2A3 on survival was analyzed by R software and Kaplan-Meier Plotter. Genomic alterations in SLC2A3 were investigated using the cBioPortal database. Coexpression of SLC2A3 was studied using LinkedOmics and STRING, and enrichment analyses were performed with R software. The relationship between SLC2A3 expression and immune infiltration was determined using TIMER and TISIDB databases. Immune checkpoints and ESTIMATE score were analyzed via the SangerBox database. Results. SLC2A3 expression was upregulated in HNSCC tissues compared to normal tissues. It was significantly related to TNM stage, histological grade, and alcohol history. High SLC2A3 expression was associated with poor prognosis in HNSCC. Coexpression analysis indicated that SLC2A3 mostly participated in the HIF-1 signaling pathway and glycolysis. Furthermore, SLC2A3 expression strongly correlated with tumor-infiltrating lymphocytes in HNSCC. Conclusion. SLC2A3 could serve as a potential prognostic biomarker for tumor immune infiltration in HNSCC.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Chu¹,

Zheng

Li³

et al. 2022

Analytical Cellular Pathology

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“…Most of the up-regulated genes (e.g., ADAM8, UPP1, SLC2A3) were related to pro-inflammatory roles, the induction of migration of immune system cells, hypoxia processes, and inflammatory diseases. [77][78][79][80][81][82] For instance, F I G U R E 4 Heatmap showing cytokines differentially expressed at a pvalue threshold of .05 in RhE samples treated with 2.3 mg/cm 2 of MW $5,000 g/mol and 5.6 mg/cm 2 of MW $15,000 g/mol. The negative control was untreated cells.…”

Section: Gene Expression Analysis Of Reconstructed Human Epidermis Modelmentioning

confidence: 99%

In vitro assessment of inflammatory skin potential of poly(methyl methacrylate) at non‐cytotoxic concentrations

Barraza‐Vergara,

Carmona‐Sarabia,

Torres‐García

et al. 2023

J Biomedical Materials Res

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Poly(methyl methacrylate) (PMMA) is considered an attractive substrate material for fabricating wearable skin sensors such as fitness bands and microfluidic devices. Despite its widespread use, inflammatory and allergic responses have been attributed to the use of this material. Therefore, the main objective of this study was to obtain a comprehensive understanding of potential biological effects triggered by PMMA at non‐cytotoxic concentrations using in vitro models of NIH3T3 fibroblasts and reconstructed human epidermis (RhE). It was hypothesized that concentrations that do not reduce cell viability are sufficient to activate pathways of inflammatory processes in the skin. The study included cytotoxicity, cell metabolism, cytokine quantification, histopathological, and gene expression analyses. The NIH3T3 cell line was used as a testbed for screening cell toxicity levels associated with the concentration of PMMA with different molecular weights (MWs) (i.e., MW ~5,000 and ~15,000 g/mol). The lower MW of PMMA had a half‐maximal inhibitory concentration (IC50) value of 5.7 mg/cm2, indicating greater detrimental effects than the higher MW (IC50 = 14.0 mg/cm2). Non‐cytotoxic concentrations of 3.0 mg/cm2 for MW ~15,000 g/mol and 0.9 mg/cm2 for MW ~5,000 g/mol) induced negative metabolic changes in NIH3T3 cells. Cell viability was severely reduced to 7% after the exposure to degradation by‐products generated after thermal and photodegradation degradation of PMMA. PMMA at non‐cytotoxic concentrations still induced overexpression of pro‐inflammatory cytokines, chemokines, and growth factors (IL1B, CXCL10, CCL5, IL1R1, IL7, IL17A, VEGFA, FGF2, IFNG, IL15) on the RhE model. The inflammatory response was also supported by histopathological and gene expression analyses of PMMA‐treated RhE, indicating tissue damage and gene overexpression. Results suggested that non‐cytotoxic concentrations of PMMA (3.0 to 5.6 mg/cm2 for MW ~15,000 g/mol and 0.9 to 2.1 mg/cm2 for MW ~5,000 g/mol) were sufficient to negatively alter NIH3T3 cells metabolism and activate inflammatory events in the RhE skin.

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“…Functionally, increased expression of GLUT1 can promote a more aggressive and glycolytic phenotype in PCa, especially in response to increased AR signaling [ 50 , 113 , 114 , 115 ]. While GLUT1 remains the most-studied glucose transporter, other family members such as GLUT3 (SLC2A3) and GLUT4 (SLC2A4) may also play a role in facilitating increased glucose uptake in advanced, treatment-resistant PCa [ 114 , 116 , 117 , 118 ].…”

Section: Major Bioenergetic Sourcesmentioning

confidence: 99%

Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer

et al. 2022

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There is an urgent need for exploring new actionable targets other than androgen receptor to improve outcome from lethal castration-resistant prostate cancer. Tumor metabolism has reemerged as a hallmark of cancer that drives and supports oncogenesis. In this regard, it is important to understand the relationship between distinctive metabolic features, androgen receptor signaling, genetic drivers in prostate cancer, and the tumor microenvironment (symbiotic and competitive metabolic interactions) to identify metabolic vulnerabilities. We explore the links between metabolism and gene regulation, and thus the unique metabolic signatures that define the malignant phenotypes at given stages of prostate tumor progression. We also provide an overview of current metabolism-based pharmacological strategies to be developed or repurposed for metabolism-based therapeutics for castration-resistant prostate cancer.

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GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors

Cited by 8 publications

References 74 publications

Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

Comprehensive Analysis of the Role of SLC2A3 on Prognosis and Immune Infiltration in Head and Neck Squamous Cell Carcinoma

In vitro assessment of inflammatory skin potential of poly(methyl methacrylate) at non‐cytotoxic concentrations

Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer

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