Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Language: Английский

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CpG‐Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2‐Mediated Remodeling of Tumor‐Associated Macrophages

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor‐associated macrophages (TAMs)into tumoricidal M1 macrophages. However, accumulation free in tumor tissues remains a substantial challenge. To address this, nanovaccine (PLGA‐CpG@ID8‐M) is engineered by encapsulating within PLGA using ID8 ovarian cancer cell membranes (ID8‐M). This demonstrates remarkable efficacy reprogramming TAMs and significantly extends survival ID8‐bearing mice. Notably, these findings indicate that also mitigate chemotherapy‐induced immunosuppression increasing proportion M1‐like reducing expression CD47 on cells, thereby achieving synergistic effect immunotherapy. Mechanistically, through transcriptome sequencing (RNA‐seq), single‐cell RNA (scRNA‐seq), mass spectrometry‐based proteomics, it elucidated enhances Gbp2 promotes recruitment Pin1, which activates NFκB signaling pathway, leading to polarization TAMs. Furthermore, with elevated inhibit growth both 4T1 breast models. Conversely, targeting diminishes antitumor vivo. study offers innovative approach immunotherapy elucidates novel mechanism (Gbp2‐Pin1‐NFκB pathway) for remodeling

Language: Английский

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The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1727 - 1727

Published: April 29, 2024

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays crucial role in driving progression, shaping treatment responses, influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) stroma, highlighting its key constituents their dynamic contributions. We examine how significant changes within cSCC ECM—specifically, alterations fibronectin, hyaluronic acid, laminins, proteoglycans, collagens—promote cancer metastasis, drug resistance. composition TME is also explored, detailing intricate interplay cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, various immune populations. These diverse players modulate development, angiogenesis, responses. Finally, we emphasize TME’s potential as therapeutic target. Emerging strategies discussed this include harnessing system (adoptive transfer, checkpoint blockade), hindering disrupting CAF activity, manipulating ECM components. approaches underscore vital that deciphering interactions advancing therapy. Further research illuminating these relationships will uncover new avenues for developing more effective treatments cSCC.

Language: Английский

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The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Oct. 7, 2024

The extracellular matrix (ECM) is a complex, dynamic network of multiple macromolecules that serve as crucial structural and physical scaffold for neighboring cells. In the tumor microenvironment (TME), ECM proteins play significant role in mediating cellular communication between cancer-associated fibroblasts (CAFs) tumor-associated macrophages (TAMs). Revealing modification TME necessitates intricate signaling cascades transpire among diverse cell populations proteins. advent single-cell sequencing has enabled identification refinement specific subpopulations, which substantially enhanced our comprehension milieu given us high-resolution perspective on diversity However, it essential to integrate data establish coherent framework. this regard, we present comprehensive review relationships ECM, TAMs, CAFs. This encompasses insights into released by TAMs CAFs, integration TAM-ECM-CAF axis, potential applications limitations targeted therapies serves reliable resource focused therapeutic strategies while highlighting intermediates TME.

Language: Английский

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Biomechanical Properties and Cellular Responses in Pulmonary Fibrosis

Bioengineering, Journal Year: 2024, Volume and Issue: 11(8), P. 747 - 747

Published: July 24, 2024

Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and transplantation, as there no curative drug for this condition. The involves excessive synthesis extracellular matrix (ECM) due to alveolar epithelial cell damage, leading scarring stiffening tissue ultimately causing respiratory failure. Although multiple factors contribute disease, exact causes remain unclear. mechanical properties tissue, including elasticity, viscoelasticity, surface tension, not affected by but also its progression. This paper reviews alteration in these pulmonary progresses how cells lung, cells, fibroblasts, macrophages, respond changes, contributing exacerbation. Furthermore, it highlights importance developing advanced vitro models, based on hydrogels 3D bioprinting, which can accurately replicate structural fibrotic lungs conducive studying effects stimuli cellular responses. review aims summarize current understanding interaction between progression alterations properties, could aid development novel therapeutic strategies disease.

Language: Английский

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Age-related meningeal extracellular matrix remodeling compromises CNS lymphatic function

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 17, 2025

Abstract Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal drainage contribute CNS accumulation dysfunction, yet underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling aged dura as a key driver CSF deficits, demonstrating peri-lymphatic collagen disrupts function. Exploring immune-derived factors contributing this ECM remodeling, transforming growth factor beta 1 (TGFβ1) major regulator using primary human dural fibroblasts. Using novel mouse model with constitutively active TGFβ receptor (TGFβR1) signaling fibroblasts, show excessive deposition impairs alters immunity. Mechanistically, reveal ECM-associated stiffness junction integrity lymphangiogenesis endothelial cells. findings establish cell fibroblast-mediated critical highlight it potential therapeutic target restoring aging.

Language: Английский

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The multifaceted roles of macrophages in the transition from hepatitis to hepatocellular carcinoma: From mechanisms to therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167676 - 167676

Published: Jan. 18, 2025

Language: Английский

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Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1212 - 1212

Published: April 2, 2025

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer, driven by either polyomavirus (MCPyV) integration or ultraviolet (UV)-induced mutations. In MCPyV-positive tumors, viral T antigens inactivate tumor suppressors pRb and p53, while virus-negative MCCs harbor UV-induced mutations that activate similar oncogenic pathways. Key signaling cascades, including PI3K/AKT/mTOR MAPK, support proliferation, survival, resistance to apoptosis. Histologically, MCC consists of small round blue cells with features, high mitotic rate, necrosis. The microenvironment (TME) plays central role in disease progression immune escape. It comprises mix tumor-associated macrophages, regulatory cytotoxic cells, elevated expression checkpoint molecules such as PD-L1, contributing an immunosuppressive niche. extracellular matrix (ECM) within the TME rich proteoglycans, collagens, metalloproteinases (MMPs), facilitating adhesion, invasion, interaction stromal cells. ECM remodeling integrin-mediated further promote evasion therapy resistance. Although inhibitors targeting PD-1/PD-L1 have shown promise treating MCC, remains major hurdle. Therapeutic strategies concurrently target TME-through inhibition components, MMPs, integrin signaling-may enhance responses improve clinical outcomes.

Language: Английский

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The Role of HER2 in Cancer and Its Influence on the Tumor Microenvironment

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

HER2 (human epidermal growth factor receptor 2) is a transmembrane tyrosine kinase that plays pivotal role in cancer progression. Overexpressed cancers such as breast, gastric, and lung cancers, contributes to aggressive tumor growth, metastasis, therapy resistance. This chapter explores HER2’s molecular functions, including its activation of key signaling pathways like PI3K/AKT MAPK, shaping the microenvironment (TME). A unique focus placed on ability reprogram TME by modulating immune suppression, activating cancer-associated fibroblasts (CAFs), enhancing angiogenesis. These interactions establish permissive environment for progression therapeutic The also discusses HER2-targeted therapies, trastuzumab, pertuzumab, antibody-drug conjugates T-DM1 T-DXd, alongside emerging strategies overcome In addition, advanced research platforms, organoids microphysiological systems (MPS), are highlighted transformative tools studying HER2-TME interactions. enable dynamic modeling ecosystem, offering unprecedented insights into HER2-driven biology precision medicine approaches. emphasizes integration MPS innovative technologies translational overcoming challenges HER2-positive cancers.

Language: Английский

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Molecular and epigenetic ex vivo profiling of testis cancer-associated fibroblasts and their interaction with germ cell tumor cells and macrophages

Matrix Biology, Journal Year: 2024, Volume and Issue: 132, P. 10 - 23

Published: June 6, 2024

Germ cell tumors (GCT) are the most common solid in young men of age 15 - 40. In previous studies, we profiled interaction GCT cells with tumor microenvironment (TM). Earlier studies showed that especially 3D fibroblasts (FB) or macrophages influenced growth behavior and cisplatin response as well transcriptome secretome cells, suggesting crosstalk these is crucial for progression therapy outcome. this study, shed light on mechanisms activation cancer-associated (CAF) setting their effects lines monocyte line THP-1. Ex vivo cultures GCT-derived CAF were established characterized molecularly epigenetically by performing DNA methylation arrays, RNA sequencing, mass spectrometry-based analysis. We demonstrated state former prevailing environment which they have resided. Hereby, postulated seminoma (SE) embryonal carcinoma (EC) activate CAF, while teratoma (TER) play only a minor role formation. turn, influence proliferation expression sensitivity-related factors polarization vitro-induced identified effector molecules IGFBP1, LGALS3BP, LYVE1, PTX3. Our data suggests vital has huge shaping extracellular matrix recruitment immune to microenvironment. conclusion, therapeutically interfering / addition standard might slow-down re-shaping TM tumor-promoting environment. Significance: The considerably influences Thus,

Language: Английский

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