CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis.

BACKGROUND: The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated in neovascularization within tumorous contexts. Nevertheless, research pertaining to the involvement of CD151 in hepatocellular carcinoma (HCC) neovascularization and its association with migrasomes remains inadequate. METHODS: To investigate the correlation between CD151 and migrasome marker TSPAN4 in liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels of CD151 were assessed in HCC tissues and correlated with patient survival outcomes. In vitro experiments were performed using HCC cell lines to evaluate the impact of CD151 expression on migrasome formation and cellular invasiveness. Cell lines with altered CD151 expression levels were utilized to study migrasome generation and in vitro invasion capabilities. Additionally, migrasome function was explored through cellular aggregation assays and phagocytosis studies. Subsequent VEGF level analysis and tissue chip experiments further confirmed the role of CD151 in mediating migrasome involvement in angiogenesis and cellular signal transduction. RESULTS: Our study revealed a significant correlation between CD151 expression and migrasome marker TSPAN4 in liver cancer, based on database analysis of clinical samples. High expression levels of CD151 were closely associated with poor survival outcomes in HCC patients. Experimentally, decreased CD151 expression led to reduced migrasome generation and diminished in vitro invasion capabilities, resulting in attenuated in vivo metastatic potential. Migrasomes were demonstrated to facilitate cellular aggregation and phagocytosis, thereby promoting cellular invasiveness. Furthermore, VEGF-enriched migrasomes were implicated in signaling and angiogenesis, accelerating HCC progression. CONCLUSIONS: In summary, our findings support the notion that elevated CD151 expression promotes migrasome formation, and migrasomes play a pivotal role in the invasiveness and angiogenesis of liver cancer cells, thereby facilitating HCC progression. This finding implies that migrasomes generated by elevated CD151 expression may constitute a promising high-priority target for anti-angiogenic therapy in HCC, offering crucial insights for the in-depth exploration of migrasome function and a renewed comprehension of the mechanism underlying liver cancer metastasis.

The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Nephrotic syndrome: Pretibial epidermolysis bullosa in a patient with CD151 tetraspanin defect: A case report.

Nephrotic syndrome (NS)-epidermolysis bullosa (EB) sensorineural deafness syndrome is an autosomal recessive rare genetic disease caused by a CD151 gene homozygous mutation on chromosome 11p15.5. In this report, we discuss a rare case related to a Saudi patient with genetic syndrome who presented with NS and EB. Whole genome sequencing results indicated a homozygous pathogenic variant identified in the CD151 gene (c.493C>T p.(Arg165*), which was consistent with a genetic diagnosis of autosomal recessive nephropathy with pretibial EB and deafness syndrome. The findings emphasize that even a single genotype can result in variable phenotypic expression, necessitating the assessment of the pleiotropic effects of the disease on the patient, which can range from severe to mild. This case report adds to the literature by highlighting the considerable phenotypic variation that can be present in patients with the CD151 mutation.

LncSUMO1P3 exacerbates malignant behaviors of esophageal squamous cell carcinoma cells via miR-486-5p/PHF8/CD151.

Background: Esophageal squamous cell carcinoma (ESCC) is a malignancy usually associated with smoking or alcohol consumption. The involvement of long noncoding RNAs (lncRNAs) in the regulation of tumor development and metastasis through molecular mechanisms has been unveiled by accumulating evidence. However, the function of lncRNA SUMO1 Pseudogene 3 (lncSUMO1P3) essential to ESCC development remains obscure. Methods: Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis were done to measure RNA and protein levels. Functional assays were carried out to examine the changes in ESCC cell phenotype. Supported by bioinformatics analysis, mechanism assays were done for assessment of putative interactions among different genes. Results: LlncSUMO1P3 was aberrantly up-regulated in ESCC cell lines, and lncSUMO1P3 deficiency could hamper cell proliferation, migration and invasion as well as epithelial-mesenchymaltransition (EMT) in ESCC while lncSUMO1P3 overexpression led to the opposite consequences. LncSUMO1P3 could competitively bind to microRNA-486-5p (miR-486-5p) or PHD finger protein 8 (PHF8) to modulate CD151 expression. CD151 was also verified to regulate ESCC cell biological behaviors. Conclusion: Our study revealed that lncSUMO1P3, up-regulated in ESCC cells, could sponge miR-486-5p and recruit PHF8 to up-regulate CD151, thus influencing the malignant behaviors of ESCC cells.

[Corrigendum] The tetraspanin CD151­ARSA mutant inhibits angiogenesis via the YRSL sequence.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 4A on p. 839, the 'CD151/24 h' and 'CD151­ARSA/48 h' panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'CD151­ARSA/48 h' panel was inadvertently placed incorrectly in the figure. The revised version of Fig. 4, now containing the correct data for the 'CD151­ARSA/48 h' experiment in Fig. 4A, is shown below. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 7: 836­842, 2013; DOI: 10.3892/mmr.2012.1250].

Role of Hemidesmosomes in Oral Carcinogenesis: A Systematic Review.

BACKGROUND: Oral cancers have limited diagnostic tools to aid clinical management. Current evidence indicates that alterations in hemidesmosomes, the adhesion complexes primarily involved in epithelial attachment to the basement membrane, are correlated to cancer phenotype for multiple cancers. This systematic review aimed to assess the experimental evidence for hemidesmosomal alterations, specifically in relation to oral potentially malignant disorders and oral squamous cell carcinomas. METHODS: We conducted a systemic review to summarise the available literature on hemidesmosomal components and their role in oral pre-cancer and cancer. Relevant studies were retrieved from a comprehensive search of Scopus, Ovid MEDLINE, Ovid Embase and Web of Science. RESULTS: 26 articles met the inclusion criteria, of which 19 were in vitro studies, 4 in vivo studies, 1 in vitro and in vivo study, and 2 in vitro and cohort studies. Among them, 15 studies discussed individual alpha-6 and/or beta-4 subunits, 12 studies discussed the alpha-6 beta-4 heterodimers, 6 studies discussed the entire hemidesmosome complex, 5 studies discussed bullous pemphigoid-180, 3 studies discussed plectin, 3 studies discussed bullous pemphigoid antigen-1 and 1 study discussed tetraspanin. CONCLUSION: Heterogeneity in cell type, experimental models, and methods were observed. Alterations in hemidesmosomal components were shown to contribute to oral pre-cancer and cancer. We conclude that there is sufficient evidence for hemidesmosomes and their components to be potential biomarkers for evaluating oral carcinogenesis.

Exploring the role of CD151 in the tumor immune microenvironment: Therapeutic and clinical perspectives.

CD151 is a transmembrane protein implicated in tumor progression and has been shown to regulate various cellular and molecular mechanisms contributing to malignancy. More recently, the role of CD151 in the tumor immune microenvironment (TIME) has gained attention as a potential target for cancer therapy. This review aims to explore the role of CD151 in the TIME, focusing on the therapeutic and clinical perspectives. The role of CD151 in regulating the interactions between tumor cells and the immune system will be discussed, along with the current understanding of the molecular mechanisms underlying these interactions. The current state of the development of CD151-targeted therapies and the potential clinical applications of these therapies will also be reviewed. This review provides an overview of the current knowledge on the role of CD151 in the TIME and highlights the potential of CD151 as a therapeutic target for cancer treatment.

Proteomic profiling and ROC analysis identify CD151 and ELAVL1 as potential therapy response markers for the antiviral drug in resistant TNBC.

Triple-negative breast cancer is high heterogeneous, aggressive, and metastatic with poor prognosis. Despite of advances in targeted therapies, TNBC has been reported to cause high morbidity and mortality. A rare subpopulation within the tumor microenvironment organized into a hierarchy of cancer stem cells is responsible for therapy resistance and tumor recurrence. Repurposing of antiviral drugs for cancer treatment is gaining momentum due to reduced cost, labour, and research time, but limited due to lack of prognostic, and predictive markers. The present study investigates proteomic profiling and ROC analysis to identify CD151 and ELAVL1 as potential therapy response markers for the antiviral drug 2-thio-6-azauridine (TAU) in resistant TNBC. The stemness of MDA-MB 231 and MDA-MD 468 adherent cells was enriched by culturing them under non-adherent and non-differentiation conditions. Then, CD151+ subpopulation was isolated and characterized for the enrichment of stemness. This study found that CD151 has overexpressed in stemness enriched subpopulations, and also showed CD44 high and CD24 low expression along with stem cell-related transcription factors octamer-binding transcription factor 4 (OCT4) and Sex determining Y-box 2 (SOX2). This study also found that TAU induced significant cytotoxicity and genotoxicity in the CD151+TNBC subpopulation and inhibited their proliferation by inducing DNA damage, cell cycle arrest at the G2M phase, and apoptosis. Further, a proteomic profiling study showed that the expression of CD151 along with ELAVL1, an RNA-binding protein, was significantly reduced with TAU treatment. KM plotter showed correlation of CD151 and ELAVL1 gene expression with a poor prognosis of TNBC. ROC analysis predicted and validated CD151 and ELAVL1 as best therapy response marker for TAU in TNBC. These findings provide new insight into repurposing antiviral drug TAU for treatment of metastatic and drug resistant TNBC.

CD151 and prostate cancer progression: A review of current literature.

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.

Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity.

Objectives: Identify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women. Methods: We performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively. Results: We identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype. Conclusions: We discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility.

Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.

Tetraspanin-enriched Microdomain Containing CD151, CD9, and TSPAN 8 - Potential Mediators of Entry and Exit Mechanisms in Respiratory Viruses Including SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, the Hubei region of China, has become a pandemic worldwide. It can transmit through droplets and enter via oral, nasal, and eye mucous membranes. It consists of single-stranded RNA (positive-sense), nonstructural proteins including enzymes and transcriptional proteins, and structural proteins such as Spike, Membrane, Envelope, and Nucleocapsid -proteins. SARS-CoV-2 mediates S-proteins entry and exit via binding to host cell surface proteins like tetraspanins. The transmembrane tetraspanins, CD151, CD9, and tetraspanin 8 (TSPAN8), facilitate the entry of novel coronaviruses by scaffolding host cell receptors and proteases. Also, CD151 was reported to increase airway hyperresponsiveness to calcium and nuclear viral export signaling. They may facilitate entry and exit by activating the serine proteases required to prime S-proteins in tetraspanin-enriched microdomains (TEMs). This article updates recent advances in structural proteins, their epitopes and putative receptors, and their regulation by proteases associated with TEMs. This review furnishes recent updates on the role of CD151 in the pathophysiology of SARS-CoV-2. We describe the role of CD151 in a possible mechanism of entry and exit in the airway, a major site for infection of SARS-CoV-2. We also updated current knowledge on the role of CD9 and TSPAN 8 in the entry and exit mechanism of coronaviruses. Finally, we discussed the importance of some small molecules which target CD151 as possible targeted therapeutics for COVID-19. In conclusion, this study could identify new targets and specific therapeutics to control emerging virus infections.

Rapid immunomagnetic co-capture assay for quantification of lung cancer associated exosomes.

Exosomes derived from biological fluids have the potential to serve as a biomarker for the early detection of various cancers. However, the lack of reliable enrichment and detection methods posed a challenge for its clinical utility. In this work, we designed a rapid co-capture-based approach for targeted enrichment and detection of lung cancer-derived exosomes from human plasma. This method relies on the formation of a sandwich complex around the exosomes that involves magnetic nanoparticles coupled to CD151 to assist in the immunomagnetic selection of lung-derived exosomes and a secondary detection antibody (CD81) coupled to horseradish peroxidase for signal amplification. The performance of the co-capture method to detect exosomes has been optimized with known exosome concentrations in human plasma and exhibited good linearity (108-105 exosomes mL-1) with a detection limit of 60.4 exosomes µL-1. This study further investigated the potential of the developed assay to differentiate healthy and lung cancer patients using 18 clinical samples by quantifying the CD151+/ CD81+ lung-derived exosomes. In conclusion, this study demonstrated a rapid co-capture-based approach that offers simultaneous isolation and detection of exosomes compatible with low sample volume for detecting lung cancer patients.

New Report of a Different Clinical Presentation of CD151 Splicing Mutation (c.351+2T>C): Could TSPAN11 be Considered as a Potential Modifier Gene for CD151?

CD151, a member of the tetraspanin family, is essential for normal development of skin and kidney. To date, only 2 pathogenic variants of the CD151 gene have been identified in a related disorder with recessive inheritance. Here, in the third study of CD151 mutations, we report 3 affected siblings presenting variable degrees of renal and dermal symptoms. Whole exome sequencing (WES) was performed on the proband, followed by data analysis and in silico assessments. Confirmation of the mutation in the other patients were carried out using Sanger sequencing. The consequence of the CD151 mutation was investigated by RNA extraction and Sanger sequencing of PCR products from cDNA. Multiple computational tools were applied for protein alignment, homology modeling, and molecular interaction analysis. WES revealed the variant c.351+2T>C, NM_139029 (GRCh37) in CD151, and this was confirmed by Sanger sequencing in all patients. This variant is the result of a substitution of nucleotide T with C that changes the position +2 of the donor splice site in intron 5, leading to total loss of exon 5 from the transcript. The mentioned variant was not found in population allele frequency databases, and prediction tools concurred in its damaging effect on the protein. Based on the criteria from ACMG guidelines, this variant is pathogenic. Interestingly, in terms of clinical findings, symptoms and severity of the disease in the patients in this study were different compared to the previous report of the mutation and the disease. In addition, in silico analysis in this study appears to suggest a candidate protein, Tetraspanin-11 (TSPAN11), that could partially modify CD151 functions. This study supports the pathogenic effect of the CD151 variant c.351+2T>C, highlights the extensive variable expressivity amongst patients, reinforces the contribution of genomic content to clinical characteristics of CD151 mutations, and accentuates the importance of modifier genes.

Basement membrane defects in CD151-associated glomerular disease.

BACKGROUND: CD151 is a cell-surface molecule of the tetraspanin family. Its lateral interaction with laminin-binding integrin ɑ3ß1 is important for podocyte adhesion to the glomerular basement membrane (GBM). Deletion of Cd151 in mice induces glomerular dysfunction, with proteinuria and associated focal glomerulosclerosis, disorganisation of GBM and tubular cystic dilation. Despite this, CD151 is not routinely screened for in patients with nephrotic-range proteinuria. We aimed to better understand the relevance of CD151 in human kidney disease. METHODS: Next-generation sequencing (NGS) was used to detect the variant in CD151. Electron and light microscopy were used to visualise the filtration barrier in the patient kidney biopsy, and immunoreactivity of patient red blood cells to anti-CD151/MER2 antibodies was performed. Further validation of the CD151 variant as disease-causing was performed in zebrafish using CRISPR-Cas9. RESULTS: We report a young child with nail dystrophy and persistent urinary tract infections who was incidentally found to have nephrotic-range proteinuria. Through targeted NGS, a novel, homozygous truncating variant was identified in CD151, a gene rarely reported in patients with nephrotic syndrome. Electron microscopy imaging of patient kidney tissue showed thickening of GBM and podocyte effacement. Immunofluorescence of patient kidney tissue demonstrated that CD151 was significantly reduced, and we did not detect immunoreactivity to CD151/MER2 on patient red blood cells. CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria, which was rescued by injection of wild-type CD151 mRNA, but not CD151 mRNA containing the variant sequence. CONCLUSIONS: Our results indicate that a novel variant in CD151 is associated with nephrotic-range proteinuria and microscopic haematuria and provides further evidence for a role of CD151 in glomerular disease. Our work highlights a functional testing pipeline for future analysis of patient genetic variants. A higher resolution version of the Graphical abstract is available as Supplementary information.

LncRNA DLGAP1-AS2 promotes the radioresistance of rectal cancer stem cells by upregulating CD151 expression via E2F1.

BACKGROUND: Radiotherapy resistance is one of the major causes of rectal cancer treatment failure. LncRNA DLGAP1-AS2 participates in the progression of several cancers. We explored the role and potential mechanism of DLGAP1-AS2 in the radioresistance of rectal cancer stem cells. METHODS: HR8348-R cells, radioresistant cells from HR8348 after irradiation, were isolated into CD133 negative (CD133-) and positive (CD133+) cells. Cell proliferation, apoptosis, migration and tumorsphere formation were determined by CCK-8, flow cytometry, wound healing assay and tumorsphere formation assay, respectively. CD133, tumor stem cell drug resistance gene (MDR1 and BCRP1), DNA repair marker (γ-H2AX) and AKT/mTOR/cyclinD1 signaling were measured by Western blot. The relationship between DLGAP1-AS2 and E2F1 was verified using RIP. The interaction between E2F1 and CD151 promoter was confirmed using dual-luciferase reporter gene assay and ChIP. AKT inhibitor API-2 was employed for validating the effect of AKT/mTOR/cyclinD1 signaling in the radioresistance of rectal cancer cells. RESULTS: The DLGAP1-AS2 level was increased in CD133+ cells after irradiation. DLGAP1-AS2 knockdown inhibited the proliferation, migration and tumorsphere formation while stimulating apoptosis in CD133+ cells. DLGAP1-AS2 inhibition downregulated the expression of CD133, MDR1, BCRP1 and γ-H2AX and suppressed AKT/mTOR/cyclinD1 activation. DLGAP1-AS2 upregulated the expression of CD151 by interacting with E2F1. API-2 neutralized the promotive effects of overexpressed CD151 on radioresistance. CONCLUSION: DLGAP1-AS2 accelerates the radioresistance of rectal cancer cells through interactions with E2F1 to upregulate CD151 expression via the activation of the AKT/mTOR/cyclinD1 pathway.

Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients.

Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.

Tetraspanins: Host Factors in Viral Infections.

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.

Nanoparticle-Aided Detection of Colorectal Cancer-Associated Glycoconjugates of Extracellular Vesicles in Human Serum.

Extracellular vesicles (EVs) are found in all biological fluids, providing potential for the identification of disease biomarkers such as colorectal cancer (CRC). EVs are heavily glycosylated with specific glycoconjugates such as tetraspanins, integrins, and mucins, reflecting the characteristics of the original cell offering valuable targets for detection of CRC. We report here on europium-nanoparticle (EuNP)-based assay to detect and characterize different surface glycoconjugates of EVs without extensive purification steps from five different CRC and the HEK 293 cell lines. The promising EVs candidates from cell culture were clinically evaluated on small panel of serum samples including early-stage (n = 11) and late-stage (n = 11) CRC patients, benign condition (n = 11), and healthy control (n = 10). The majority of CRC cell lines expressed tetraspanin sub-population and glycovariants of integrins and conventional tumor markers. The subpopulation of CD151 having CD63 expression (CD151CD63) was significantly (p = 0.001) elevated in early-stage CRC (8 out of 11) without detecting any benign and late-stage samples, while conventional CEA detected mostly late-stage CRC (p = 0.045) and with only four early-stage cases. The other glycovariant assays such as CEACon-A, CA125WGA, CA 19.9Ma696, and CA 19.9Con-A further provided some complementation to the CD151CD63 assay. These results indicate the potential application of CD151CD63 assay for early detection of CRC patients in human serum.