Biomolecules最新文献_第5页

FUS::DDIT3 Fusion Protein in the Development of Myxoid Liposarcoma and Possible Implications for Therapy. FUS::DDIT3融合蛋白在肌样脂肪肉瘤发展中的作用及对治疗的可能影响

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-14 DOI: 10.3390/biom14101297

Xutong Hou, Wenjin Shi, Wenxin Luo, Yuwen Luo, Xuelin Huang, Jing Li, Ning Ji, Qianming Chen

{"title":"FUS::DDIT3 Fusion Protein in the Development of Myxoid Liposarcoma and Possible Implications for Therapy.","authors":"Xutong Hou, Wenjin Shi, Wenxin Luo, Yuwen Luo, Xuelin Huang, Jing Li, Ning Ji, Qianming Chen","doi":"10.3390/biom14101297","DOIUrl":"10.3390/biom14101297","url":null,"abstract":"The FUS::DDIT3 fusion protein, formed by the chromosomal translocation t (12;16) (q13;p11), is found in over 90% of myxoid liposarcoma (MLS) cases and is a crucial protein in its development. Many studies have explored the role of FUS::DDIT3 in MLS, and the prevailing view is that FUS::DDIT3 inhibits adipocyte differentiation and promotes MLS growth and invasive migration by functioning as an aberrant transcription factor that affects gene expression and regulates its downstream molecules. As fusion proteins are gradually showing their potential as targets for precision cancer therapy, FUS::DDIT3 has also been investigated as a therapeutic target. Drugs that target FUS::DDIT3 and its downstream molecules for treating MLS are widely utilized in both clinical practice and experimental studies, and some of them have demonstrated promising results. This article reviews the findings of relevant research, providing an overview of the oncogenic mechanisms of the FUS::DDIT3 fusion protein in MLS, as well as recent advancements in its therapy.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Myelin Debris-Treated Microglial Cell Lines Activates the Gene Expression of Cholesterol Efflux Transporter ABCA1. 抑制髓鞘碎片处理的小胶质细胞系中的胆固醇储存酶 ACAT1/SOAT1 可激活胆固醇外排转运体 ABCA1 的基因表达。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-14 DOI: 10.3390/biom14101301

Thao N Huynh, Matthew C Havrda, George J Zanazzi, Catherine C Y Chang, Ta Yuan Chang

{"title":"Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Myelin Debris-Treated Microglial Cell Lines Activates the Gene Expression of Cholesterol Efflux Transporter ABCA1.","authors":"Thao N Huynh, Matthew C Havrda, George J Zanazzi, Catherine C Y Chang, Ta Yuan Chang","doi":"10.3390/biom14101301","DOIUrl":"https://doi.org/10.3390/biom14101301","url":null,"abstract":"Aging is the major risk factor for Alzheimer's disease (AD). In the aged brain, myelin debris accumulates and is cleared by microglia. Phagocytosed myelin debris increases neutral lipid droplet content in microglia. Neutral lipids include cholesteryl esters (CE) and triacylglycerol (TAG). To examine the effects of myelin debris on neutral lipid content in microglia, we added myelin debris to human HMC3 and mouse N9 cells. The results obtained when using 3H-oleate as a precursor in intact cells reveal that myelin debris significantly increases the biosynthesis of CE but not TAG. Mass analyses have shown that myelin debris increases both CE and TAG. The increase in CE biosynthesis was abolished using inhibitors of the cholesterol storage enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1/SOAT1). ACAT1 inhibitors are promising drug candidates for AD treatment. In myelin debris-loaded microglia, treatment with two different ACAT1 inhibitors, K604 and F12511, increased the mRNA and protein content of ATP-binding cassette subfamily A1 (ABCA1), a protein that is located at the plasma membrane and which controls cellular cholesterol disposal. The effect of the ACAT1 inhibitor on ABCA1 was abolished by preincubating cells with the liver X receptor (LXR) antagonist GSK2033. We conclude that ACAT1 inhibitors prevent the accumulation of cholesterol and CE in myelin debris-treated microglia by activating ABCA1 gene expression via the LXR pathway.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes. Yap是一种对氨基酸L-异亮氨酸敏感的营养传感器，能调节心肌细胞中Ctgf的表达。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-14 DOI: 10.3390/biom14101299

Victoria L Nelson, Ashley L Eadie, Lester Perez, Malav Madhu, Mathew Platt, Angella Mercer, Thomas Pulinilkunnil, Petra Kienesberger, Jeremy A Simpson, Keith R Brunt

{"title":"Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes.","authors":"Victoria L Nelson, Ashley L Eadie, Lester Perez, Malav Madhu, Mathew Platt, Angella Mercer, Thomas Pulinilkunnil, Petra Kienesberger, Jeremy A Simpson, Keith R Brunt","doi":"10.3390/biom14101299","DOIUrl":"https://doi.org/10.3390/biom14101299","url":null,"abstract":"Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)-a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the Complexities of Hereditary Angioedema. 揭开遗传性血管性水肿的复杂面纱。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-14 DOI: 10.3390/biom14101298

Cristina Violeta Tutunaru, Oana Maria Ică, George G Mitroi, Carmen Daniela Neagoe, George F Mitroi, Olguța Anca Orzan, Beatrice Bălăceanu-Gurău, Simona Laura Ianoși

{"title":"Unveiling the Complexities of Hereditary Angioedema.","authors":"Cristina Violeta Tutunaru, Oana Maria Ică, George G Mitroi, Carmen Daniela Neagoe, George F Mitroi, Olguța Anca Orzan, Beatrice Bălăceanu-Gurău, Simona Laura Ianoși","doi":"10.3390/biom14101298","DOIUrl":"https://doi.org/10.3390/biom14101298","url":null,"abstract":"Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represents about 5% to 10% of cases, is often estrogen-dependent and although several mutations have been identified, it typically involves normal C1-INH activity. Despite the differences in C1-INH functionality, all three types of HAE manifest with similar clinical symptoms. HAE leads to recurrent episodes of non-pruritic angioedema, which occurs in the absence of urticaria. Breakthroughs in understanding HAE pathophysiology have revolutionized treatment, leading to the development of highly targeted therapies for both acute management and long-term prevention. Meanwhile, cutting-edge advancements in omics technologies are unlocking new possibilities for biomarker discovery, paving the way for more precise diagnoses and personalized treatment strategies that could significantly enhance patient outcomes. This review will delve into the intricate pathophysiology, diverse clinical presentations, and diagnostic challenges of HAE while exploring emerging biomarkers and innovative approaches to therapeutic management and prevention strategies. Additionally, it will underscore the vital importance of screening family members of affected individuals, even when symptoms are not present.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the Potential of Phytocannabinoids: Exploring Marijuana's Lesser-Known Constituents for Neurological Disorders. 揭示植物大麻素的潜力：探索大麻中治疗神经系统疾病的鲜为人知的成分。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-13 DOI: 10.3390/biom14101296

Balapal S Basavarajappa, Shivakumar Subbanna

{"title":"Unveiling the Potential of Phytocannabinoids: Exploring Marijuana's Lesser-Known Constituents for Neurological Disorders.","authors":"Balapal S Basavarajappa, Shivakumar Subbanna","doi":"10.3390/biom14101296","DOIUrl":"https://doi.org/10.3390/biom14101296","url":null,"abstract":"Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms. Beyond Δ9-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood-brain barrier (BBB) effectively. Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ9-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders. This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive Analysis of the 5xFAD Mouse Model of Alzheimer's Disease Using dMRI, Immunohistochemistry, and Neuronal and Glial Functional Metabolic Mapping. 利用 dMRI、免疫组织化学以及神经元和神经胶质功能代谢图谱对 5xFAD 阿尔茨海默病小鼠模型进行全面分析。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-13 DOI: 10.3390/biom14101294

Emil W Westi, Saba Molhemi, Caroline Termøhlen Hansen, Christian Stald Skoven, Rasmus West Knopper, Dashne Amein Ahmad, Maja B Rindshøj, Aishat O Ameen, Brian Hansen, Kristi A Kohlmeier, Blanca I Aldana

{"title":"Comprehensive Analysis of the 5xFAD Mouse Model of Alzheimer's Disease Using dMRI, Immunohistochemistry, and Neuronal and Glial Functional Metabolic Mapping.","authors":"Emil W Westi, Saba Molhemi, Caroline Termøhlen Hansen, Christian Stald Skoven, Rasmus West Knopper, Dashne Amein Ahmad, Maja B Rindshøj, Aishat O Ameen, Brian Hansen, Kristi A Kohlmeier, Blanca I Aldana","doi":"10.3390/biom14101294","DOIUrl":"https://doi.org/10.3390/biom14101294","url":null,"abstract":"Alzheimer's disease (AD) is characterized by complex interactions between neuropathological markers, metabolic dysregulation, and structural brain changes. In this study, we utilized a multimodal approach, combining immunohistochemistry, functional metabolic mapping, and microstructure sensitive diffusion MRI (dMRI) to progressively investigate these interactions in the 5xFAD mouse model of AD. Our analysis revealed age-dependent and region-specific accumulation of key AD markers, including amyloid-beta (Aβ), GFAP, and IBA1, with significant differences observed between the hippocampal formation and upper and lower regions of the cortex by 6 months of age. Functional metabolic mapping validated localized disruptions in energy metabolism, with glucose hypometabolism in the hippocampus and impaired astrocytic metabolism in the cortex. Notably, increased cortical glutaminolysis suggested a shift in microglial metabolism, reflecting an adaptive response to neuroinflammatory processes. While dMRI showed no significant microstructural differences between 5xFAD and wild-type controls, the study highlights the importance of metabolic alterations as critical events in AD pathology. These findings emphasize the need for targeted therapeutic strategies addressing specific metabolic disturbances and underscore the potential of integrating advanced imaging with metabolic and molecular analyses to advance our understanding of AD progression.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells. 二硫仑、姜黄素和二氯乙酸钠对脱氨三磷酸异构酶的选择性抑制：Jurkat 细胞中 T 细胞急性淋巴细胞白血病的协同治疗策略。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-13 DOI: 10.3390/biom14101295

Luis A Flores-López, Ignacio De la Mora-De la Mora, Claudia M Malagón-Reyes, Itzhel García-Torres, Yoalli Martínez-Pérez, Gabriela López-Herrera, Gloria Hernández-Alcántara, Gloria León-Avila, Gabriel López-Velázquez, Alberto Olaya-Vargas, Saúl Gómez-Manzo, Sergio Enríquez-Flores

{"title":"Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells.","authors":"Luis A Flores-López, Ignacio De la Mora-De la Mora, Claudia M Malagón-Reyes, Itzhel García-Torres, Yoalli Martínez-Pérez, Gabriela López-Herrera, Gloria Hernández-Alcántara, Gloria León-Avila, Gabriel López-Velázquez, Alberto Olaya-Vargas, Saúl Gómez-Manzo, Sergio Enríquez-Flores","doi":"10.3390/biom14101295","DOIUrl":"10.3390/biom14101295","url":null,"abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin. 设计和合成 MDA-9/Syntenin 的小分子探针。

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-12 DOI: 10.3390/biom14101287

Nehru Viji Sankaranarayanan, Bharath Kumar Villuri, Balaji Nagarajan, Sarah Lewicki, Swadesh K Das, Paul B Fisher, Umesh R Desai

引用次数: 0

Human Herpesvirus-6B Infection and Alterations of Gut Microbiome in Patients with Fibromyalgia: A Pilot Study. 人类疱疹病毒-6B 感染与纤维肌痛患者肠道微生物组的改变：一项试点研究

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-12 DOI: 10.3390/biom14101291

Lauma Ievina, Nikita Fomins, Dita Gudra, Viktorija Kenina, Anda Vilmane, Sabine Gravelsina, Santa Rasa-Dzelzkaleja, Modra Murovska, Davids Fridmanis, Zaiga Nora-Krukle

{"title":"Human Herpesvirus-6B Infection and Alterations of Gut Microbiome in Patients with Fibromyalgia: A Pilot Study.","authors":"Lauma Ievina, Nikita Fomins, Dita Gudra, Viktorija Kenina, Anda Vilmane, Sabine Gravelsina, Santa Rasa-Dzelzkaleja, Modra Murovska, Davids Fridmanis, Zaiga Nora-Krukle","doi":"10.3390/biom14101291","DOIUrl":"https://doi.org/10.3390/biom14101291","url":null,"abstract":"Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain often accompanied by fatigue, sleep disturbances, memory issues, and mood disorders. The exact cause of FM remains unknown, and diagnosis is typically based on a history of persistent widespread pain, as there are no objective biomarkers usable in diagnosis of this disorder available. The aim of this study was to identify measurable indicators specific to FM with potential as biomarkers. This study included 17 individuals diagnosed with FM and 24 apparently healthy persons. Using real-time polymerase chain reaction (qPCR), we detected the presence of human herpesvirus (HHV)-6A and B genomic sequences in DNA isolated from peripheral blood mononuclear cells (PBMCs) and buccal swabs. HHV-6-specific IgG and IgM class antibodies, along with proinflammatory cytokine levels, were measured using enzyme-linked immunosorbent assay (ELISA) and bead-based multiplex assays. Additionally, the gut microbiome was analyzed through next-generation sequencing. HHV-6B was more frequently detected in the PBMCs of FM patients. FM patients with a body mass index (BMI) of 30 or higher exhibited elevated cytokine levels compared to the control group with the same BMI range. Gut microbiome analysis revealed significant differences in both α-diversity and β-diversity between the FM and control groups, indicating a shift in species abundance in the FM group.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity. 在随机定位过程中形成稳定的肺肿瘤球体涉及雌激素敏感性的增加

IF 4.8 2区生物学

Biomolecules Pub Date : 2024-10-12 DOI: 10.3390/biom14101292

Balkis Barkia, Viviann Sandt, Daniela Melnik, José Luis Cortés-Sánchez, Shannon Marchal, Bjorn Baselet, Sarah Baatout, Jayashree Sahana, Daniela Grimm, Markus Wehland, Herbert Schulz, Manfred Infanger, Armin Kraus, Marcus Krüger

{"title":"The Formation of Stable Lung Tumor Spheroids during Random Positioning Involves Increased Estrogen Sensitivity.","authors":"Balkis Barkia, Viviann Sandt, Daniela Melnik, José Luis Cortés-Sánchez, Shannon Marchal, Bjorn Baselet, Sarah Baatout, Jayashree Sahana, Daniela Grimm, Markus Wehland, Herbert Schulz, Manfred Infanger, Armin Kraus, Marcus Krüger","doi":"10.3390/biom14101292","DOIUrl":"https://doi.org/10.3390/biom14101292","url":null,"abstract":"The formation of tumor spheroids on the random positioning machine (RPM) is a complex and important process, as it enables the study of metastasis ex vivo. However, this process is not yet understood in detail. In this study, we compared the RPM-induced spheroid formation of two cell types of lung carcinoma (NCI-H1703 squamous cell carcinoma cells and Calu-3 adenocarcinoma cells). While NCI-H1703 cells were mainly present as spheroids after 3 days of random positioning, Calu-3 cells remained predominantly as a cell layer. We found that two-dimensional-growing Calu-3 cells have less mucin-1, further downregulate their expression on the RPM and therefore exhibit a higher adhesiveness. In addition, we observed that Calu-3 cells can form spheroids, but they are unstable due to an imbalanced ratio of adhesion proteins (β1-integrin, E-cadherin) and anti-adhesion proteins (mucin-1) and are likely to disintegrate in the shear environment of the RPM. RPM-exposed Calu-3 cells showed a strongly upregulated expression of the estrogen receptor alpha gene ESR1. In the presence of 17β-estradiol or phenol red, more stable Calu-3 spheroids were formed, which was presumably related to an increased amount of E-cadherin in the cell aggregates. Thus, RPM-induced tumor spheroid formation depends not solely on cell-type-specific properties but also on the complex interplay between the mechanical influences of the RPM and, to some extent, the chemical composition of the medium used during the experiments.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0