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Fleur Schaper, Annemiek B van Spriel
Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME). In particular, environmental signals (for instance, soluble factors or cell-cell contact) transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9) are widely and broadly expressed, others (CD53, CD37, Tssc6) have an expression pattern restricted to hematopoietic cells...
2018: Frontiers in Immunology
Joshua S Brzozowski, Danielle R Bond, Helen Jankowski, Belinda J Goldie, Rachel Burchell, Crystal Naudin, Nathan D Smith, Christopher J Scarlett, Martin R Larsen, Matthew D Dun, Kathryn A Skelding, Judith Weidenhofer
To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo to both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 and CD151) have altered expression patterns in many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed to determine whether EVs from prostate cells with altered CD9 and CD151 expression could influence cellular behaviour and increase the metastatic capabilities of non-tumourigenic prostate cells...
June 11, 2018: Scientific Reports
Luise Florin, Thorsten Lang
Tetraspanins (Tspans) are a family of four-span transmembrane proteins, known as plasma membrane "master organizers." They form Tspan-enriched microdomains (TEMs or TERMs) through lateral association with one another and other membrane proteins. If multiple microdomains associate with each other, larger platforms can form. For infection, viruses interact with multiple cell surface components, including receptors, activating proteases, and signaling molecules. It appears that Tspans, such as CD151, CD82, CD81, CD63, CD9, Tspan9, and Tspan7, coordinate these associations by concentrating the interacting partners into Tspan platforms...
2018: Frontiers in Immunology
Chin-An Yang, Hsi-Yuan Huang, Ju-Chen Yen, Jan-Gowth Chang
The nucleotide degrading enzyme gene RNASEH2A (ribonuclease H2 subunit A) has been found to be overexpressed in cancers. Our aim was to understand the role of RNASEH2A in cancer prognostication and to establish a scoring system based on the expressions of genes interacting with RNASEH2A. We screened the nucleotide degrading enzyme gene expression in RNAseq data of 14 cancer types derived from The Cancer Genome Atlas (TCGA) and found that RNASEH2A overexpression was associated with poor patient survival only in renal cell carcinomas (RCCs)...
May 28, 2018: International Journal of Molecular Sciences
N V Yunusova, E A Tugutova, S N Tamkovich, I V Kondakova
Major (CD9, CD63, CD81) and others (CD82, CD151, Tspan8) tetraspanins are widely represented in exosomes, where they interact with various proteins and form functional tetraspanin complexes. Tetraspanin complexes include proteases. Tetraspanin-associated exosomal proteases (ADAM proteases, MMPs, EMMPRIN) play an important role in the processes of cell motility, migration, invasion and formation of metastases. Also, a significant contribution to tumor progression is made by proteases that are not associated with tetraspanins...
March 2018: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Claire Mennan, John Garcia, Helen McCarthy, Sharon Owen, Jade Perry, Karina Wright, Robin Banerjee, James B Richardson, Sally Roberts
Objective To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2 ) or continuous hypoxia (2% O2 ). Design Chondrocytes were extracted from patients undergoing total knee replacement ( n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (3D) pellet culture and compared with freshly isolated chondrocytes (FC). Cells were assessed by flow cytometry for markers indicative of mesenchymal stromal cells (MSCs), chondrogenic-potency and dedifferentiation...
April 1, 2018: Cartilage
Yanru Zhao, Mengwen Yan, Chen Chen, Wei Gong, Zhongwei Yin, Huaping Li, Jiahui Fan, Xin A Zhang, Dao Wen Wang, Houjuan Zuo
Heart failure (HF) is the final common pathway of various cardiovascular diseases. Although it is well documented that reduction of cardiac angiogenesis contributes to the progression from adaptive cardiac hypertrophy to HF, the molecular mechanisms remain unknown. In the present study, we found that cardiac expression of miR-124 was increased in patients and mice with HF. Recombinant adeno-associated virus (rAAV)-mediated miR-124 over-expression aggravated angiotensin II (Ang II) infusion-induced cardiac dysfunction and abnormal cardiac angiogenesis in mice...
March 6, 2018: Oncotarget
Rama Rao Malla, Santhi Pandrangi, Seema Kumari, Murali Mohan Gavara, Anil Kumar Badana
Exosomes are cell-cell communicators emerging as a new paradigm for noninvasive diagnosis and prognosis of treatment response. Exosomal tetraspanin proteins like CD63, CD9 and CD81 play a critical role in sorting, selective recruitment of biomolecules, target selection, cell-specific entry, capturing, angiogenesis and vasculogenesis. These tetraspanins are being used as markers for oral, colorectal and colon cancers and glioblastoma. However, exosomal markers with robust specificity for early detection of carcinomas are the furthest along...
March 25, 2018: Asia-Pacific Journal of Clinical Oncology
Yajie Yu, Chao Liang, Shangqian Wang, Jundong Zhu, Chenkui Miao, Yibo Hua, Meiling Bao, Qiang Cao, Chao Qin, Pengfei Shao, Zengjun Wang
Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated in various malignant cell types. However, the function of CD151 and its underlying mechanism in renal cell carcinoma is still unknown. In this study, we detected the expression of CD151 in RCC cells and tissues and explored its regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma tissues and cells and its expression was significantly associated with tumor stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays...
March 2, 2018: Oncotarget
Vera S Donnenberg, Jayce Jieming Zhang, Erika Moravcikova, Ernest Michael Meyer, Haihui Lu, Christian T Carson, Albert D Donnenberg
Flow cytometric cell surface proteomics provides a new and powerful tool to determine changes accompanying neoplastic transformation and invasion, providing clues to essential interactions with the microenvironment as well as leads for potential therapeutic targets. One of the most important advantages of flow cytometric cell surface proteomics is that it can be performed on living cells that can be sorted for further characterization and functional studies. Here, we document the surface proteome of clonogenic metastatic breast cancer (MBrCa) explants, which was strikingly similar to that of normal mesenchymal stromal cells (P = 0...
April 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Zhen Kang, Enhua Xiao
Cluster of differentiation (CD)151, a member of tetraspanin family, is considered to be the first tetraspanin to be associated with tumor metastasis. Previous studies in vivo , in vitro and in the clinic have demonstrated that CD151 is involved in tumor progression at different levels through interaction with integrins, growth factor receptors and matrix metalloproteinases. Transcatheter arterial chemoembolization (TACE) is widely recommended for the treatment of patients with advanced hepatocellular carcinoma (HCC) worldwide...
January 2018: Oncology Letters
Eliana Amati, Omar Perbellini, Gianluca Rotta, Martina Bernardi, Katia Chieregato, Sabrina Sella, Francesco Rodeghiero, Marco Ruggeri, Giuseppe Astori
BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking...
January 16, 2018: Stem Cell Research & Therapy
Yongkang Qiao, Yan Yan, Kai Sen Tan, Sheryl S L Tan, Ju Ee Seet, Thiruma Valavan Arumugam, Vincent T K Chow, De Yun Wang, Thai Tran
BACKGROUND: Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. OBJECTIVES: We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains...
December 21, 2017: Journal of Allergy and Clinical Immunology
Crystal Naudin, Brian Smith, Danielle R Bond, Matthew D Dun, Rodney J Scott, Leonie K Ashman, Judith Weidenhofer, Séverine Roselli
In humans and FVB/N mice, loss of functional tetraspanin CD151 is associated with glomerular disease characterised by early onset proteinuria and ultrastructural thickening and splitting of the glomerular basement membrane (GBM). To gain insight into the molecular mechanisms associated with disease development, we characterised the glomerular gene expression profile at an early stage of disease progression in FVB/N Cd151-/- mice compared to Cd151+/+ controls. This study identified 72 up-regulated and 183 down-regulated genes in FVB/N Cd151-/- compared to Cd151+/+ glomeruli (p < 0...
November 22, 2017: Scientific Reports
Hassan Vahidnezhad, Leila Youssefian, Amir Hossein Saeidian, Hamid Reza Mahmoudi, Andrew Touati, Maryam Abiri, Abdol-Mohammad Kajbafzadeh, Sophia Aristodemou, Lu Liu, John A McGrath, Adam Ertel, Eric Londin, Ariana Kariminejad, Sirous Zeinali, Paolo Fortina, Jouni Uitto
Epidermolysis bullosa (EB) is caused by mutations in as many as 19 distinct genes. We have developed a next-generation sequencing (NGS) panel targeting genes known to be mutated in skin fragility disorders, including tetraspanen CD151 expressed in keratinocytes at the dermal-epidermal junction. The NGS panel was applied to a cohort of 92 consanguineous families of unknown subtype of EB. In one family, a homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) at the exon 5/intron 5 border was identified, and RT-PCR and whole transcriptome analysis by RNA-seq confirmed deletion of the entire exon 5 encoding 25 amino acids...
November 11, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
Kun Zhao, Ulrike Erb, Thilo Hackert, Margot Zöller, Shijing Yue
The tetraspanin Tspan8 supports via associated integrins and proteases tumor progression and angiogenesis. To shed light on its activities in non-transformed cells, we generated a Tspan8 knockout (ko) mouse, comparing leukocyte migration, angiogenesis, wound healing and tumor growth with wild type, CD151ko and Tspan8/CD151ko (dbko) mice. CD151ko mice were included as CD151 activities resemble that of Tspan8, and dbko mice to exclude mutual substitution. Tspan8ko and dbko mice show no pathological phenotype...
February 2018: Biochimica et Biophysica Acta
Kasinath Viswanathan, Marieke C Verweij, Nessy John, Daniel Malouli, Klaus Früh
Human cytomegalovirus (HCMV) depends on and modulates multiple host cell membrane proteins during each stage of the viral life cycle. To gain a global view of the impact of HCMV-infection on membrane proteins, we analyzed HCMV-induced changes in the abundance of membrane proteins in fibroblasts using stable isotope labeling with amino acids (SILAC), membrane fractionation and protein identification by two-dimensional liquid chromatography and tandem mass spectrometry. This systematic approach revealed that CD81, CD44, CD98, caveolin-1 and catenin delta-1 were down-regulated during infection whereas GRP-78 was up-regulated...
2017: PloS One
J Castillo, V Bernard, F A San Lucas, K Allenson, M Capello, D U Kim, P Gascoyne, F C Mulu, B M Stephens, J Huang, H Wang, A A Momin, R O Jacamo, M Katz, R Wolff, M Javle, G Varadhachary, I I Wistuba, S Hanash, A Maitra, H Alvarez
Background: Detection of circulating tumor DNA can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We carried out a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal 'surfaceome' in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Lillian Seu, Christopher Tidwell, Laura Timares, Alexandra Duverger, Frederic H Wagner, Paul A Goepfert, Andrew O Westfall, Steffanie Sabbaj, Olaf Kutsch
The tetraspanin CD151 is a marker of aggressive cell proliferation and invasiveness for a variety of cancer types. Given reports of CD151 expression on T cells, we explored whether CD151 would mark T cells in a hyperactivated state. Consistent with the idea that CD151 could mark a phenotypically distinct T cell subset, it was not uniformly expressed on T cells. CD151 expression frequency was a function of the T cell lineage (CD8 > CD4) and a function of the memory differentiation state (naive T cells < central memory T cells < effector memory T cells < T effector memory RA+ cells)...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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