Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix?

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 824 - 824

Published: March 28, 2023

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and tissue extracellular matrix (ECM). It composed of disaccharides containing glucuronic acid N-acetylglucosamine, synthesized by HA synthase (HAS) enzymes degraded hyaluronidase (HYAL) or reactive oxygen nitrogen species (ROS/RNS) actions. deposited as high molecular weight (HMW) polymer low (LMW) fragments oligosaccharides. affects biological functions interacting with HA-binding proteins (hyaladherins). HMW anti-inflammatory, immunosuppressive, antiangiogenic, whereas LMW has pro-inflammatory, pro-angiogenetic, oncogenic effects. ROS/RNS degrade HA, albeit at enhanced levels during injury inflammatory processes. Thus, degradation endothelial glycocalyx increased ROS challenges vascular integrity can initiate several disease progressions. Conversely, exerts vital role in wound healing through ROS-mediated modifications, which affect innate immune system. The normal turnover protects against rigidification. Insufficient leads rigidity, leading dysfunction. Both endogenous exogenous have scavenging capacity ROS. interactions are more complex than presently perceived present an important research topic.

Language: Английский

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The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 8, 2022

Hypoxia is an environmental stressor that instigated by low oxygen availability. It fuels the progression of solid tumors driving tumor plasticity, heterogeneity, stemness and genomic instability. metabolically reprograms microenvironment (TME), adding insult to injury acidic, nutrient deprived poorly vascularized conditions act dampen immune cell function. Through its impact on key cancer hallmarks creating a physical barrier conducive survival, hypoxia modulates escape from mounted response. The cell-immune crosstalk in context hypoxic TME tips balance towards cold immunosuppressed resistant checkpoint inhibitors (ICI). Nonetheless, evidence emerging could make asset for improving response ICI. Tackling contexture has taken silico , digitalized approach with increasing number studies applying bioinformatics deconvolute cellular non-cellular elements TME. Such approaches have additionally been combined signature-based proxies further dissect turbulent hypoxia-immune relationship. In this review we will be highlighting mechanisms which impacts functions how translate predicting immunotherapy era machine learning computational biology.

Language: Английский

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CD44: a cancer stem cell marker and therapeutic target in leukemia treatment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 26, 2024

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. can mediate the interaction between leukemic stem cells surrounding extracellular matrix, thereby inducing cascade of signaling pathways to regulate their various behaviors. In this review, we focus on impact CD44s/CD44v as biomarkers leukemia development discuss current research prospects for CD44-related interventions clinical application.

Language: Английский

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Receptor-Targeted Nanomedicine for Cancer Therapy

Receptors, Journal Year: 2024, Volume and Issue: 3(3), P. 323 - 361

Published: July 3, 2024

Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have potential to be targeted by nanocarrier systems We also highlight different types ligands researchers explored. Our discussion covers various modalities, including small molecules, aptamers, peptides, antibodies, cell-based strategies, focuses clinical developments. Additionally, article highlights challenges arise during translation nanocarrier-based strategies. It provides future directions improving research area clinically translatable cancer-targeted therapy improve treatment efficacy while minimizing toxicity.

Language: Английский

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The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15812 - 15812

Published: Oct. 31, 2023

Hyaluronic acid (HA) receptor CD44 is widely used for identifying cancer stem cells and its activation promotes stemness. Recent evidence shows that overexpression of associated with poor prognosis in most human cancers mediates therapy resistance. For these reasons, recent years, has become a treatment target precision oncology, often via HA-conjugated antineoplastic drugs. Importantly, HA molecules different sizes have dual effect and, therefore, may enhance or attenuate the CD44-mediated signaling pathways, as they compete endogenous binding to receptors. The magnitude effects could be crucial progression, well driving inflammatory response tumor microenvironment. increasingly common use drugs HA-based compounds adjuvants treatment, adds further complexity understanding net hyaluronan-CD44 cancers. In this review, I focus on significance malignancy discuss dichotomous function hyaluronan/CD44 axis progression.

Language: Английский

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A Novel Anti-CD44 Variant 9 Monoclonal Antibody C44Mab-1 Was Developed for Immunohistochemical Analyses against Colorectal Cancers

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(4), P. 3658 - 3673

Published: April 20, 2023

Cluster of differentiation 44 (CD44) is a type I transmembrane glycoprotein and has been shown to be cell surface marker cancer stem-like cells in various cancers. In particular, the splicing variants CD44 (CD44v) are overexpressed cancers play critical roles stemness, invasiveness, resistance chemotherapy radiotherapy. Therefore, understanding function each CD44v indispensable for CD44-targeting therapy. CD44v9 contains variant 9-encoded region, its expression predicts poor prognosis patients with plays malignant progression tumors. promising target diagnosis Here, we developed sensitive specific monoclonal antibodies (mAbs) against by immunizing mice CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO/CD44v3–10) cells. We first determined their epitopes using enzyme-linked immunosorbent assay characterized applications as flow cytometry, western blotting, immunohistochemistry. One established clones, C44Mab-1 (IgG1, kappa), reacted peptide indicating that recognizes CD44v9. could recognize CHO/CD44v3–10 or colorectal lines (COLO201 COLO205) cytometric analysis. The apparent dissociation constant (KD) CHO/CD44v3–10, COLO201, COLO205 was 2.5 × 10−8 M, 3.3 6.5 respectively. Furthermore, able detect CD44v3–10 blotting endogenous immunohistochemistry tissues. These results indicated useful detecting not only cytometry but also

Language: Английский

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Development of a Novel Anti-CD44 Variant 5 Monoclonal Antibody C44Mab-3 for Multiple Applications against Pancreatic Carcinomas

Antibodies, Journal Year: 2023, Volume and Issue: 12(2), P. 31 - 31

Published: April 28, 2023

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and resistance conventional chemotherapy. CD44 has been known as stem cell marker plays tumor promotion drug roles in various cancers. In particular, splicing variants are overexpressed many carcinomas play essential stemness, invasiveness or metastasis, treatments. Therefore, understanding each variant’s (CD44v) function distribution is for establishment CD44-targeting therapy. this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary (CHO)-K1 cells established anti-CD44 monoclonal antibodies (mAbs). One clones (C44Mab-3; IgG1, kappa) recognized peptides variant-5-encoded region, indicating that C44Mab-3 specific mAb CD44v5. Moreover, reacted CHO/CD44v3–10 pancreatic lines (PK-1 PK-8) by flow cytometry. The apparent KD PK-1 was 1.3 × 10−9 M 2.6 M, respectively. could detect exogenous CD44v3–10 endogenous CD44v5 Western blotting stained formalin-fixed paraffin-embedded but not normal epithelial immunohistochemistry. These results indicate useful detecting applications expected be application diagnosis

Language: Английский

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A Narrative Review on CD44’s Role in Glioblastoma Invasion, Proliferation, and Tumor Recurrence

Cancers, Journal Year: 2023, Volume and Issue: 15(19), P. 4898 - 4898

Published: Oct. 9, 2023

High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in tumor with inevitable recurrence. GBM recurrence may be caused by glioma stem-like cells (GSCs) that survive many kinds therapy. GSCs high expression levels CD44 are highly invasive resistant to radio-chemotherapy. multifunctional molecule promotes the invasion proliferation via various signaling pathways. Among these, paired pathways reciprocally activate under different hypoxic conditions. Severe hypoxia (0.5-2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, cMET, all related migration invasion. In contrast, moderate (2.5-5% HIF-2α, such as vascular endothelial growth (VEGF)/VEGFR2, cMYC, cyclin D1. All these genes proliferation. Oxygen environments around can change before after resection. Before resection, oxygen concentration at periphery severely hypoxic. reparative stage cavity shows hypoxia. These observations suggest upregulated severe promote cells. Conversely, when leads hypoxia, HIF-2α genes. The phenotypic transition regulated leading dichotomy between according conditions, play crucial role

Language: Английский

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CD44: A New Prognostic Marker in Colorectal Cancer?

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1569 - 1569

Published: April 19, 2024

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It overexpressed in several types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit CSC traits, such as self-renewal, epithelial-mesenchymal transition (EMT) capability, and resistance to chemo- radiotherapy. The role maintaining stemness the function tumor progression accomplished by binding its main ligand, hyaluronan (HA). HA-CD44 complex activates signaling pathways that lead proliferation, adhesion, migration, invasion. gene regularly undergoes alternative splicing, resulting standard (CD44s) variant (CD44v) isoforms. different functional roles CD44s specific CD44v isoforms still need be fully understood. clinicopathological impact promoting tumorigenesis suggests could molecular target for therapy. Furthermore, recent association observed between KRAS-dependent carcinomas potential correlations mutational burden (TMB) microsatellite instability (MSI) open new research scenarios developing strategies treatment. This review summarises current regarding isoform structures, their roles, functions supporting discusses therapeutic implications.

Language: Английский

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CD44 and its implication in neoplastic diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(6)

Published: May 23, 2024

CD44, a nonkinase single span transmembrane glycoprotein, is major cell surface receptor for many other extracellular matrix components as well classic markers of cancer stem cells and immune cells. Through alternative splicing

Language: Английский

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