Proteoglycan research最新文献

Structural Features of Glypicans and their Impact on Wnt Signaling in Cancer. Glypicans的结构特征及其对癌症中Wnt信号传导的影响。

Proteoglycan research Pub Date : 2025-04-01 Epub Date: 2025-05-13 DOI: 10.1002/pgr2.70029

Hsi-En Tsao, Mitchell Ho

{"title":"Structural Features of Glypicans and their Impact on Wnt Signaling in Cancer.","authors":"Hsi-En Tsao, Mitchell Ho","doi":"10.1002/pgr2.70029","DOIUrl":"10.1002/pgr2.70029","url":null,"abstract":"Glypicans (GPCs) are a family of cell surface proteoglycans involved in multiple signaling pathways that regulate cell fate and proliferation. They share a characteristic structure composed of a core protein with two or more heparan sulfate chains and a glycosyl-phosphatidylinositol anchor that attaches them to the cell membrane. Aberrant expression of certain glypicans such as GPC1, GPC2, and GPC3 has been found in multiple types of cancer and causes the dysregulation of Wnt, hedgehog, and other signaling pathways, making them emerging targets for cancer immunotherapy. The molecular mechanism by which glypicans interact with signaling factors will provide insights for the development of cancer therapeutics. However, the structural complexes of human glypicans with Wnt and other key signaling factors remain unsolved. In this brief review, we analyze the current protein structural evidence for glypicans, with an emphasis on their interaction with Wnt, in an effort to provide insights to understand the molecular mechanisms by which glypicans play positive or negative roles in Wnt signaling in cancer and to discuss their translational potentials.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of Heparin Interactions With Recombinant Rodent Stabilin-2/Hyaluronic Acid Receptor for Endocytosis (HARE). 肝素与重组鼠稳定素-2/透明质酸内吞受体（HARE）相互作用的表征。

Proteoglycan research Pub Date : 2025-04-01 Epub Date: 2025-04-07 DOI: 10.1002/pgr2.70027

Reed A Rohr, Evan A Schroder, Joseph D Staab, William P Singh, Callan J Schroder, Grant D Hatcher, Joshua T McWilliams, Jiyuan Yang, Abby E Bopp, Linda B Fatumoju, Zhangjie Wang, Jonathan S Dordick, Robert J Linhardt, Fuming Zhang, Jian Liu, Edward N Harris

{"title":"Characterization of Heparin Interactions With Recombinant Rodent Stabilin-2/Hyaluronic Acid Receptor for Endocytosis (HARE).","authors":"Reed A Rohr, Evan A Schroder, Joseph D Staab, William P Singh, Callan J Schroder, Grant D Hatcher, Joshua T McWilliams, Jiyuan Yang, Abby E Bopp, Linda B Fatumoju, Zhangjie Wang, Jonathan S Dordick, Robert J Linhardt, Fuming Zhang, Jian Liu, Edward N Harris","doi":"10.1002/pgr2.70027","DOIUrl":"10.1002/pgr2.70027","url":null,"abstract":"Stabilin-2 is the primary scavenger for hyaluronan (HA) and binds to over two dozen other ligands including chondroitin sulfates, heparin, oxidized/acetylated LDL, etc. Although rat liver sinusoidal endothelial cells are the preferred primary cell lines and animal for physiological studies of Stab2/HARE, the rat recombinant protein has never been characterized. Since the rat Stab2/HARE has a high degree homology to mouse Stab2/HARE which has been cloned, our hypothesis is that the rat receptor is identical to mouse and very similar to the human receptor. Rat Stab2/HARE was cloned and expressed in the FlpIn HEK293 cell line. The recombinant protein was analyzed for HA and heparin binding/endocytosis as well as synthetic heparin (Dekaparin) in a mouse knockout model. The secreted ecto-domain was also created for surface plasmon resonance analysis. The physical structure of rat Stab2/HARE is different than human in that the small isoform is not expressed as robustly and reduction of the protein results in what is likely two physical conformational forms. Rat Stab2/HARE binding strength with HA is weaker when compared to human Stab2/HARE, but rate of endocytosis is higher. Heparin-Stab2/HARE bonding strength is similar to human, though endocytic rate tends to be higher. Metabolism of Dekaprin is delayed in a Stab2KO mouse model and affects liver sequestration of this drug. Rat Stab2/HARE has similar properties as the human Stab2/HARE with the exceptions that the rat recombinant protein has a different physical structure and has an increased HA and heparin internalization rate.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12393792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 investigation of proteoglycan gene expression in breast cancer: Discovery of a unique proteoglycan gene signature linked to the malignant phenotype. 乳腺癌中蛋白聚糖基因表达的综合研究：发现与恶性表型相关的独特蛋白聚糖基因特征。

Proteoglycan research Pub Date : 2025-01-01 Epub Date: 2025-01-08 DOI: 10.1002/pgr2.70014

Simone Buraschi, Gabriel Pascal, Federico Liberatore, Renato V Iozzo

{"title":"Comprehensive investigation of proteoglycan gene expression in breast cancer: Discovery of a unique proteoglycan gene signature linked to the malignant phenotype.","authors":"Simone Buraschi, Gabriel Pascal, Federico Liberatore, Renato V Iozzo","doi":"10.1002/pgr2.70014","DOIUrl":"10.1002/pgr2.70014","url":null,"abstract":"Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due to their diverse roles in cancer progression. Their unique ability to interact with specific membrane receptors, growth factors, and cytokines provides a promising avenue for the development of recombinant proteoglycan-based therapies that could enhance the precision and efficacy of cancer treatment. In this study, we performed a comprehensive analysis of the proteoglycan gene landscape in human breast carcinomas. Leveraging the available wealth of genomic and clinical data regarding gene expression in breast carcinoma and using a machine learning model, we identified a unique gene expression signature composed of five proteoglycans differentially modulated in the tumor tissue: Syndecan-1 and asporin (upregulated) and decorin, PRELP and podocan (downregulated). Additional query of the breast carcinoma data revealed that serglycin, previously shown to be increased in breast carcinoma patients and mouse models and to correlate with a poor prognosis, was indeed decreased in the vast majority of breast cancer patients and its levels inversely correlated with tumor progression and invasion. This proteoglycan gene signature could provide novel diagnostic capabilities in breast cancer biology and highlights the need for further utilization of publicly available datasets for the clinical validation of preclinical experimental results.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alveolar glycocalyces during health and critical illness. 健康和危重疾病期间的肺泡糖萼。

Proteoglycan research Pub Date : 2025-01-01 Epub Date: 2025-03-05 DOI: 10.1002/pgr2.70022

Yimu Yang, Eric P Schmidt

引用次数: 0

TMEM2: A New Dimension in Hyaluronan Biology. TMEM2：透明质酸生物学的新维度。

Proteoglycan research Pub Date : 2025-01-01 Epub Date: 2025-02-25 DOI: 10.1002/pgr2.70021

Yu Yamaguchi

引用次数: 0

Chemoenzymatic synthesis with the Pasteurella hyaluronan synthase; production of a multitude of defined authentic, derivatized, and analog polymers. 巴氏杆菌透明质酸合成酶的化学酶合成生产大量的定义真实的，衍生的，和模拟聚合物。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-10-06 DOI: 10.1002/pgr2.70000

Paul L DeAngelis

{"title":"Chemoenzymatic synthesis with the Pasteurella hyaluronan synthase; production of a multitude of defined authentic, derivatized, and analog polymers.","authors":"Paul L DeAngelis","doi":"10.1002/pgr2.70000","DOIUrl":"10.1002/pgr2.70000","url":null,"abstract":"Hyaluronan (HA; [-3-GlcNAc-1-beta-4-GlcA-1-beta] n ), an essential matrix polysaccharide of vertebrates and the molecular camouflage coating in certain pathogens, is polymerized by \"HA synthase\" (HAS) enzymes. Three HAS classes have been identified with biotechnological utility, but only the Class II PmHAS from Pasteurella multocida Type A has been useful for preparation of very defined HA polymers in vitro. Two general chemoenzymatic strategies with different size products are possible: (1) repetitive step-wise extension reactions by sequential addition of a single monosaccharide from a donor UDP-sugar onto an acceptor (or \"primer\") comprised of a short glycosaminoglycan chain (e.g., HA di-, tri- or tetrasaccharide) or an artificial glucuronide yielding homogeneous oligosaccharides in the range of 2 to ~20 monosaccharide units (n = 1 to ~10), or (2) \"one-pot\" polymerization reactions employing acceptor-mediated synchronization with stoichiometric size control yielding quasi-monodisperse (i.e., polydispersity approaching 1; very narrow size distributions) polysaccharides in the range of ~7 kDa to ~2 MDa (n = ~17 to 5000). In either strategy, acceptors containing non-carbohydrate functionalities (e.g., biotin, fluorophores, amines) can add useful moieties to the reducing termini of HA chains at 100% efficiency. As a further structural diversification, PmHAS can utilize a variety of unnatural UDP-sugar analogs thus adding novel groups (e.g., trifluoroacetyl, alkyne, azide, sulfhydryl) along the HA backbone and/or at its nonreducing terminus. This review discusses the current understanding and recent advances in HA chemoenzymatic synthesis methods using PmHAS. This powerful toolbox has potential for creation of a multitude of HA-based probes, therapeutics, drug conjugates, coatings, and biomaterials.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer. glypican-3相互作用伙伴的蛋白质组学图谱：甲胎蛋白和其他细胞外蛋白作为肝癌潜在免疫治疗靶点的鉴定

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-10-06 DOI: 10.1002/pgr2.70004

Yi-Fan Zhang, Shaoli Lin, Xiao Zhen, Mitchell Ho

{"title":"A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer.","authors":"Yi-Fan Zhang, Shaoli Lin, Xiao Zhen, Mitchell Ho","doi":"10.1002/pgr2.70004","DOIUrl":"10.1002/pgr2.70004","url":null,"abstract":"Antibody and cell-based therapeutics targeting cell surface receptors have emerged as a major class of immune therapeutics for treating cancer. However, the number of cell surface targets for cancer immunotherapy remains limited. Glypican-3 (GPC3) is a cell surface proteoglycan and an oncofetal antigen. In this study, we report a large-scale tumor-associated GPC3 co-immunoprecipitation (CoIP)-proteomic study using liver cancer xenograft tumors in mice. We identified 153 GPC3-associated proteins through mass spectrometry. To identify potential drug targets, we categorized GPC3-associated proteins based on their subcellular locations using UniProt annotations, with a focus on extracellular proteins. Additionally, we annotated differentially expressed proteins in hepatocellular carcinoma (HCC) versus non-tumor liver samples based on the literature, analyzed expression levels in tumor versus normal tissues using TCGA and GTEx databases via GEPIA, and identified prognostic liver cancer markers according to GEPIA. Among GPC3-associated proteins, Immunoglobulin Superfamily Member 1 (IGSF1), alpha-fetoprotein (AFP), FAT Atypical Cadherin 1 (FAT1), Formin 1 (FMN1), and Guanylate Cyclase 2C (GUCY2C), were identified as potential therapeutic targets. Furthermore, we validated the direct protein interaction between GPC3 and AFP through immunoprecipitation with purified proteins and through co-localization imaging using immunofluorescence microscopy. This study provides large proteomic datasets related to GPC3-associated proteins, enhancing our understanding of glypican biology in cancer cells and offering a new approach to identifying immunotherapy targets.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling. 作为病理细胞外基质重塑生物标志物的可溶性蛋白聚糖和蛋白聚糖片段。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-16 DOI: 10.1002/pgr2.70011

Marsioleda Kemberi, Alexander F Minns, Salvatore Santamaria

引用次数: 0

High-fidelity and iterative affinity extraction of hyaluronan. 透明质酸的高保真迭代亲和提取。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-12-06 DOI: 10.1002/pgr2.70008

Dorothea A Erxleben, Felipe Rivas, Ian Smith, Suruchi Poddar, Paul L DeAngelis, Elaheh Rahbar, Adam R Hall

引用次数: 0

Injury From Nematode Lung Migration Induces an IL-13-Dependent Hyaluronan Matrix. 线虫肺迁移造成的损伤诱导了一种依赖于 IL-13 的透明质酸基质

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-25 DOI: 10.1002/pgr2.70012

Rebecca J Dodd, Dora Moffatt, Monika Vachiteva, James E Parkinson, Brian H K Chan, Anthony J Day, Judith E Allen, Tara E Sutherland

{"title":"Injury From Nematode Lung Migration Induces an IL-13-Dependent Hyaluronan Matrix.","authors":"Rebecca J Dodd, Dora Moffatt, Monika Vachiteva, James E Parkinson, Brian H K Chan, Anthony J Day, Judith E Allen, Tara E Sutherland","doi":"10.1002/pgr2.70012","DOIUrl":"10.1002/pgr2.70012","url":null,"abstract":"A consistent feature of lung injury is a rapid and sustained accumulation of hyaluronan (HA). The rodent gut-dwelling nematode Nippostrongylus brasiliensis (Nb) induces tissue damage as it migrates through the lungs. Type 2 immune responses are essential for the repair of the lungs, hence Nb infection is a well-established model to study immune-mediated lung repair. We found that Nb infection was associated with increased HA in the lung, which peaked at d7 post-infection (p.i.). Deposition of HA in the alveolar epithelium correlated with regions of damaged tissue and the type 2 immune response, which is characterized by eosinophilia and increased type 2 cytokines such as IL-13. Consistent with the accumulation of HA, we observed increased expression of the major synthase Has2, alongside decreased expression of Hyal1, Hyal2, and Tmem2, which can degrade existing HA. Expression of Tsg6 was also increased and correlated with the presence of inter-α-inhibitor heavy chain-HA complexes (HC·HA) at d7 p.i. Using IL-13-deficient mice, we found that the accumulation of HA during Nb infection was IL-13 dependent. Our data thus provide further evidence that IL-13 is a modulator of the HA matrix during lung challenge and links IL-13-mediated HA regulation to tissue repair pathways.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":"e70012"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0