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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DNA‐based Precision Tools to Probe and Program Mechanobiology and Organ Engineering

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

DNA nanotechnology represents an innovative discipline that combines with biotechnology. It exploits the distinctive characteristics of deoxyribonucleic acid (DNA) to create nanoscale structures and devices remarkable accuracy functionality. Researchers may complex nanostructures precision specialized functions using DNA's innate stability, adaptability, capacity self-assemble through complementary base-pairing interactions. Integrating multiple disciplines, known as nanobiotechnology, allows production sophisticated nanodevices a broad range applications. These include precise drug delivery systems, extremely sensitive biosensors, construction intricate tissue scaffolds for regenerative medicine. Moreover, combining mechanobiology provides new understanding how small-scale mechanical stresses molecular interactions affect cellular activity development. has potential revolutionize diagnostics, engineering, organ regeneration. This could lead enormous improvements in biomedicine. review emphasizes most recent developments nanotechnology, explicitly highlighting its significant influence on growing involvement engineering. extensive overview present trends, obstacles, future prospects this fast-progressing area.

Language: Английский

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Cellular elasticity in cancer: a review of altered biomechanical features

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(22), P. 5299 - 5324

Published: Jan. 1, 2024

A large number of studies have shown that changes in biomechanical characteristics are an important indicator tumor transformation normal cells. Elastic deformation is one the more studied features cells, which plays role tumourigenesis and development. Altered cell elasticity often brings many indications. This manuscript reviews effects altered cellular on characteristics, including adhesion viscosity, migration, proliferation, differentiation stiffness. Also, physical factors may affect elasticity, such as temperature, height, cell-viscosity, aging, summarized. Then, cell-matrix, cytoskeleton, vitro culture medium, cell-substrate with different three-dimensional structures during tumorigenesis outlined. Importantly, we summarize current signaling pathways well tests for elastic deformation. Finally, hybrid materials: polymer-polymer, protein-protein, protein-polymer hybrids, also, nano-delivery strategies target resilience cases at least clinical phase 1 trials. Overall, behavior cancer modulated by biological, chemical, changes, turn potential to alter this be encouraging prediction future discovery therapies.

Language: Английский

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The role of LSM1 in breast cancer: Shaping metabolism and tumor-associated macrophage infiltration

Pharmacological Research, Journal Year: 2023, Volume and Issue: 198, P. 107008 - 107008

Published: Nov. 22, 2023

LSM1 is part of the cytoplasmic protein complex Lsm1-7-Pat1 and likely involved in pre-mRNA degradation by aiding U4/U6 snRNP formation. More research needed to uncover LSM1's potential breast cancer (BRCA) clinical pathology, tumor immune microenvironment, precision oncology. We discovered as a diagnostic marker for advanced BRCA with poor survival, using multi-omics approach. studied expression across regions its link cells through various methods, including spatial transcriptomics single-cell RNA-sequencing. also examined how silencing affects mitochondrial function energy metabolism environment. These findings were confirmed 54 patient biopsies tissue microarrays. Immunofluorescence bioinformatics assessed connection clinicopathological features prognosis. This study uncovers gene patterns linked cancer, macrophage processes. Silencing disrupts mitochondria metabolism. Spatial analysis aligns previous results, showing macrophages. Biopsies confirm elevation increased presence. To summarize, changes may drive progression, making it prognostic marker. It influences tumor's environment during metastasis, promise medicine drug screening BRCA.

Language: Английский

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The role of matrix stiffness in breast cancer progression: a review

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Oct. 17, 2023

The significance of matrix stiffness in cancer development has been investigated recent years. gradual elastic force the extracellular imparts to cells, known as stiffness, is one most important types mechanical stimulation. Increased alters biological activity which promotes growth numerous malignancies, including breast cancer. Comprehensive studies have demonstrated that increasing activates molecular signaling pathways are closely linked progression. There many articles exploring relationship between mechanism hardness and cancer, so we wanted provide a systematic summary research advances. In this review, briefly introduce elaborate on effect behavior pathways, finally, will talk about treatment focuses stiffness.

Language: Английский

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Management of B3 breast lesions: potential clinical implications from a retrospective study conducted in an accredited Breast Unit following the 2024 EUSOMA guidelines

European Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 109579 - 109579

Published: Jan. 1, 2025

Language: Английский

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Collagen architecture in triple negative breast cancer

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(5), P. e0324655 - e0324655

Published: May 21, 2025

This study evaluated collagen properties in TNBC samples collected from different racial groups to determine the presence of variance matrix architecture. African American (AA) breast cancer patients have a significantly higher mortality rate and nearly three-fold increased prevalence triple negative (TNBC) when compared Caucasian (C) patients. The extracellular region surrounding tumors contains abundant fibers, these fibers undergo remodeling throughout progression, promote metastasis, impede treatment response. High mammographic density, commonly known as dense tissue, is hypothesized be more prevalent AA women characterized by deposition associated with aggressive cancers. aim this research was investigate fibrillar architecture C using two-photon microscopy second harmonic generation (SHG), an intrinsic optical signal produced collagen. Twenty tissue regions per tumor sample were randomly selected for SHG microscopy, image processing conducted Fiji macro TWOMBLI quantify mesoscopic morphological nanoscopic Forward-Backward ratio. Compared images samples, those exhibited significant increase parameters including fiber area, total length, number endpoints branchpoints, but had decreased lacunarity. Collagen microstructure, fibril arrangement packing did not differ between groups. These results illustrate that analyzed may macrostructural characteristics phenotype formation.

Language: Английский

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Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 27, 2024

Abstract Background Over the last two decades, tumor-derived RNA expression signatures have been developed for most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction treatment decision-making. In this context, molecular gained by main components of tumor microenvironment, such as cancer-associated fibroblasts (CAFs), explored prognostic therapeutic tools. Nevertheless, a deeper understanding significance CAFs-related gene cancers still remains be disclosed. Methods sequencing technology (RNA-seq) was employed profile compare transcriptome CAFs isolated from patients affected tumors. The differentially expressed genes (DEGs) characterizing were intersected with data public datasets derived bulk RNA-seq profiles patients. Pathway enrichment analyses allowed us appreciate biological DEGs. K-means clustering applied construct specific cancer stratify independent cohorts into high low clusters. Kaplan-Meier survival curves log-rank tests predict differences parameters clusters Decision-tree analysis used validate results boosting calculations then obtained decision-tree algorithm. Results Data assess signature that includes 8 ( ITGA11 , THBS1 FN1 EMP1 ITGA2 FYN SPP1 EMP2 ) belonging pro-metastatic signaling routes, focal adhesion pathway. Survival indicated cluster showing aforementioned displays worse clinical outcomes. Next, we identified 11 IL13RA2 GDF7 IL33 CXCL1 TNFRSF19 CXCL6 LIFR CXCL5 IL7 TSLP TNFSF15 associated immune responses. A these predictive poor rates significantly validated through two-step approach, based on unsupervised (clustering) supervised (classification) learning techniques, accuracy (≥ 90%) cohorts. Conclusion We huge heterogeneity transcriptional Of note, novel might considered reliable indicators valuable biomarkers better management

Language: Английский

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Licochalcone A from licorice reprograms metabolic and antioxidant pathways in the breast leading to a tumor preventive environment

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Abstract Background Anti-estrogens have had limited impact on breast cancer (BC) prevention. Novel agents with better tolerability, and efficacy beyond estrogen receptor (ER) positive BC are needed. We studied licochalcone A (LicA) for ER-agnostic Methods evaluated antiproliferative effects of LicA in seven cell lines its suppression ER+ ER− xenograft tumors mice. High-risk human tissue was treated ex vivo , followed by RNA sequencing metabolism flux modeling. Confirmatory testing performed an independent specimen set ER+/− using NanoString metabolic panel, proteomics, western blots, spatiotemporally resolved cholesterol quantification single cells. Results suppressed proliferation vitro tumor growth . It downregulated pivotal steps PI3K-AKT-SREBP1-dependent lipogenesis, PI3K AKT phosphorylation, SREBP1 protein expression, levels the plasma membrane inner leaflet, to normal also prostaglandin E2 synthesis PRPS1-catalyzed de novo nucleotide biosynthesis, stalling proliferation; further evident reduced MKI67 BCL2 proteins. Conclusions targets SREBP1, a central regulator lipogenesis immune response, reducing pro-tumorigenic aberrations lipid homeostasis inflammation. is promising non-endocrine candidate

Language: Английский

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Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?

Neuro-Oncology, Journal Year: 2024, Volume and Issue: 27(1), P. 33 - 49

Published: Sept. 16, 2024

Abstract The field of immunology has traditionally focused on immune checkpoint modulation adaptive cells. However, many malignancies such as glioblastoma are mostly devoid T cells and rather enriched with immunosuppressive myeloid the innate system. While some targets shared between immunity, myeloid-specific checkpoints could also serve potential therapeutics. To better understand impact blockade cells, we systematically summarize current literature focusing direct immunological effects PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, CXCL10/CXCR3. By synthesizing molecular mechanisms translational implications, aim to prioritize agents in this category therapeutics for glioblastoma.

Language: Английский

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