Targeting heparanase/heparan sulfate proteoglycans by non‐anticoagulant heparins: Opportunities for innovative therapeutic approaches in sarcomas DOI Creative Commons
Cinzia Lanzi, Sandro Pasquali, Giuliana Cassinelli

и другие.

Proteoglycan Research, Год журнала: 2024, Номер 2(4)

Опубликована: Окт. 1, 2024

Abstract Sarcomas are a heterogeneous group of aggressive mesenchymal malignancies. They account for 1% all tumors in the general population and 15–20% pediatric age young adults. Despite differences histology pathobiology, diverse types sarcomas traditionally managed with common multi‐modal approach including surgery, radiotherapy, polychemotherapy. Unfortunately, prognosis advanced or recurrent disease remains poor. Moreover, rarity high cellular, molecular, genetic/epigenetic heterogeneity make identification therapeutic targets challenging. Therefore it an urgent need to identify effective therapies improve patients' outcome. Common peculiar biological motifs deregulation growth factor signaling, proangiogenic promigratory pathways, tumor‐microenviroment interactions, transcriptional epigenetic machinery, differentiation program, provide actionable dependencies exploitable intervention. Among these, deregulated heparan sulfate proteoglycan system due aberrant expression key components as well structural/functional modifications mediated by endosulfatases endoβ‐ d ‐glycosidase heparanase, is emerging crucial player tumor progression valuable target across different sarcoma subtypes. In preclinical studies, non‐anticoagulant heparins have been shown counteract metastatic dissemination various models according their mimetic anti‐heparanase activities. Heparin derivatives also improved anti‐sarcoma efficacy molecularly targeted agents cytotoxic drugs. this minireview, we summarize current knowledge about interplay between heparanase/heparan pathways involved sarcomagenesis progression. We illustrate understanding mechanisms action contribution anti‐heparanase, anti‐receptor tyrosine kinase, likely immunomodulatory activities effects. Finally, discuss few aspects worthy exploration highlighting how elucidation underpinning antitumor heparin contexts may suggest new vulnerabilities approaches.

Язык: Английский

Extracellular matrix-induced signaling pathways in mesenchymal stem/stromal cells DOI Creative Commons
E. S. Novoseletskaya, П. В. Евдокимов, Anastasia Efimenko

и другие.

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 19, 2023

Abstract The extracellular matrix (ECM) is a crucial component of the stem cell microenvironment, or stem-cell niches, and contributes to regulation behavior fate. Accumulating evidence indicates that different types cells possess large variety molecules responsible for interactions with ECM, mediating specific epigenetic rearrangements corresponding changes in transcriptome profile. Signals from ECM are at all stages ontogenesis, including embryonic postnatal development, as well tissue renewal repair. could regulate transition quiescent state readiness perceive signals differentiation induction (competence) between (commitment). Currently, unveil complex networks cellular signaling multiple approaches screening methods, analysis matrixome, creation predictive protein–protein based on experimental data used. In this review, we consider existing regarded contribution ECM-induced intracellular pathways into focusing mesenchymal stem/stromal (MSCs) well-studied type totally depended ECM. Furthermore, propose system biology-based approach prediction ECM-mediated signal transduction target cells.

Язык: Английский

Процитировано

24
Targeting glypican 3 by Immunotoxins; the promise of immunotherapy in hepatocellular carcinoma DOI
Elham Rismani, Nikoo Hossein‐Khannazer, Moustapha Hassan

и другие.

Expert Opinion on Therapeutic Targets, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Introduction Tumor cell's resistance, high recurrence rate, and low overall survival rate have made hepatocellular carcinoma (HCC) a major health concern. The combination of advanced targeted therapies such as immunotherapy, with conventional treatments has gained traction for application on HCC. Immunotoxins (ITs) represent category biomolecules that combine the affinity antibodies cytotoxic properties toxins.

Язык: Английский

Процитировано

1
Global impact of proteoglycan science on human diseases DOI Creative Commons
Christopher Xie, Liliana Schaefer, Renato V. Iozzo

и другие.

iScience, Год журнала: 2023, Номер 26(11), С. 108095 - 108095

Опубликована: Окт. 4, 2023

Язык: Английский

Процитировано

17
Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy DOI Creative Commons
Maurizio Mongiat, Gabriel J. Pascal, Evelina Poletto

и другие.

Proteoglycan Research, Год журнала: 2024, Номер 2(3)

Опубликована: Июнь 29, 2024

Anti-angiogenic therapy is an established method for the treatment of several cancers and vascular-related diseases. Most agents employed target vascular endothelial growth factor A, major cytokine stimulating angiogenesis. However, efficacy these treatments limited by onset drug resistance. Therefore, it fundamental importance to better understand mechanisms that regulate angiogenesis microenvironmental cues play significant role influence patient outcome. In this context, here we review three basement membrane heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin collagen XVIII. These HSPGs are abundantly expressed in vasculature and, due their complex molecular architecture, they interact with multiple cell receptors, deeply affecting function. Under normal conditions, exert pro-angiogenic functions. pathological conditions such as cancer inflammation, extracellular matrix remodeling leads degradation large precursor molecules liberation bioactive processed fragments displaying potent angiostatic activity. unexpected functions have been demonstrated C-terminal perlecan XVIII, endorepellin endostatin. can also induce autophagy cells which contributes angiostasis. Overall, affect counterbalancing signals during tumor progression, represent possible means develop new prognostic biomarkers novel therapeutic approaches solid tumors.

Язык: Английский

Процитировано

6
Endothelial Dysfunction and Cardiovascular Disease: Hyperbaric Oxygen Therapy as an Emerging Therapeutic Modality? DOI Creative Commons
Tanja Batinac, Lara Batičić,

Antea Kršek

и другие.

Journal of Cardiovascular Development and Disease, Год журнала: 2024, Номер 11(12), С. 408 - 408

Опубликована: Дек. 19, 2024

Maintaining the physiological function of vascular endothelium and endothelial glycocalyx is crucial for prevention cardiovascular disease, which one leading causes morbidity mortality worldwide. Damage to these structures can lead atherosclerosis, hypertension, other problems, especially in individuals with risk factors such as diabetes obesity. Endothelial dysfunction associated ischemic disease has a negative impact on overall health. The aim this review was comprehensively summarize role health thrombo-inflammatory conditions. It highlights how dysfunction, influenced by diabetes, chronic kidney obesity, leads adverse outcomes, including heart failure. Recent evidence suggests that hyperbaric oxygen therapy (HBOT) may offer therapeutic benefits treatment disease. This presents current mechanisms HBOT promotes angiogenesis, shows antimicrobial immunomodulatory effects, enhances antioxidant defenses, stimulates stem cell activity. latest findings important topics will be presented, effects cardiac function, plaque stability, integrity. In addition, alleviating aging, glucose metabolism regulation discussed, along its inflammation potential benefit ischemia–reperfusion injury. While demonstrates significant potential, also addresses risks excessive oxidative stress toxicity. By combining information molecular maintenance homeostasis, provides valuable insights into development innovative strategies aimed at protecting restoring prevent treat diseases.

Язык: Английский

Процитировано

3
Functional Targeting of Glypican-4 by a Conformation-Specific Single-Domain Antibody DOI

Remi BONJEAN,

Brigitte Kerfélec, Patrick Chames

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Dichotomous Effects of Glypican-4 on Cancer Progression and Its Crosstalk with Oncogenes DOI Open Access

Victor Hansson,

Fang Cheng, Grigorios Georgolopoulos

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3945 - 3945

Опубликована: Апрель 2, 2024

Glypicans are linked to various aspects of neoplastic behavior, and their therapeutic value has been proposed in different cancers. Here, we have systematically assessed the impact GPC4 on cancer progression through functional genomics transcriptomic analyses across a broad range Survival analysis using TCGA patient data reveals divergent effects expression types, revealing elevated levels be associated with both poor favorable prognoses cancer-dependent manner. Detailed investigation role glioblastoma non-small cell lung adenocarcinoma by genetic perturbation studies displays opposing these cancers, where knockout CRISPR/Cas9 attenuated proliferation augmented cells overexpression exhibited significant opposite effect. Further, GPC4-knocked-down restored proliferation, indicating its mitogenic effect this type. Additionally, survival substantiated findings, an association between prognosis glioblastoma, while outcome carcinoma patients. Finally, analysis, attempted assign mechanisms action GPC4, as find it implicated cycle control core pathways. The revealed upregulation oncogenes, including FGF5, TGF-β superfamily members, ITGA-5 which were downregulated Our findings illuminate pleiotropic cancer, underscoring potential putative prognostic biomarker implications type dependent

Язык: Английский

Процитировано

2
GPC3-mediated metabolic rewiring of diabetic mesenchymal stromal cells enhances their cardioprotective functions via PKM2 activation DOI Creative Commons

Darukeshwara Joladarashi,

Charan Thej,

Vandana Mallaredy

и другие.

iScience, Год журнала: 2024, Номер 27(10), С. 111021 - 111021

Опубликована: Сен. 24, 2024

Язык: Английский

Процитировано

2
Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation DOI Creative Commons
Anna K. Koster, Oleg Yarishkin, Adrienne E. Dubin

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(41)

Опубликована: Окт. 2, 2024

The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into plasma membrane respond to indentation or stretching lipid bilayer, thus converting mechanical forces signals that can be interpreted by cells, in form calcium flux changes potential. While PIEZO participate diverse physiological processes, from sensing shear stress blood flow vasculature detecting touch through mechanoreceptors skin, molecular details enable these mechanosensors tune their responses over a vast dynamic range remain largely uncharacterized. To survey landscape surrounding at cell surface, we employed mass spectrometry-based proteomic approach capture identify extracellularly exposed proteins vicinity PIEZO1. This PIEZO1-proximal interactome was enriched surface localized junctions signaling hubs within membrane. Functional screening interaction candidates imaging electrophysiology an overexpression system identified adhesion molecule CADM1/SynCAM slows inactivation kinetics with little effect on PIEZO2. Conversely, found CADM1 knockdown accelerates endogenous Neuro-2a cells. Systematic deletion domains indicates transmembrane region is critical for observed effects PIEZO1, suggesting modulation mediated interactions near bilayer.

Язык: Английский

Процитировано

2
Targeting glypicans through EGFR and JAK/STAT signaling axes drives breast cancer progression DOI Creative Commons
Paraskevi Ioannou, Kyriaki Tzaferi, Christos Koutsakis

и другие.

Proteoglycan Research, Год журнала: 2024, Номер 2(1)

Опубликована: Янв. 1, 2024

Abstract Extracellular matrix (ECM) and its dynamic remodeling contribute to the progression of breast cancer, most prevailing cancer type in women. Glypicans (GPCs) function as cell co‐receptors by facilitating formation ligand–receptor complexes. An important regulator context is JAK/STAT signaling pathway that oversees expression genes associated with characteristics. Epidermal growth factor receptor (EGFR) a pivotal player this process. The aim study examine effect EGFR pathways on GPCs cells different estrogen (ER) status, depicting subtypes. To end, ERα‐positive MCF‐7, ERβ‐positive MDA‐MB‐231 lines were evaluated terms impact downstream inhibition both functional properties well 1‐6 genes. Notably, cascades mitigate proliferation migration, while increasing adhesion collagen I an ER‐independent manner. However, exhibited cell‐line‐dependent GPC expression, MCF‐7 mostly downregulated excepting GPC‐4 GPC‐5. Conversely, cells, activation essential for maintaining at low levels. Additionally, STRING analysis identified small leucine‐rich PG decorin putative link between all EGFR. Subsequently, deeper understanding may shed light into role interplay progression, thus contributing novel therapeutic solutions.

Язык: Английский

Процитировано

1