Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 11, 2023

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation distant metastasis. Anticancer treatments including adjuvant therapies targeted are effective in eliminating cancer cells but limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role development through changes macromolecule components, degradation enzymes stiffness. These variations under control cellular components tissue via aberrant activation signaling pathways, interaction ECM to multiple surface receptors, mechanical impact. Additionally, shaped regulates immune which results suppressive microenvironment hinders efficacy immunotherapies. Thus, acts as barrier protect from supports progression. Nevertheless, profound regulatory network remodeling hampers design individualized antitumor treatment. Here, we elaborate on composition ECM, discuss specific mechanisms remodeling. Precisely, highlight impact development, proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, escape. Finally, emphasize "normalization" potential strategy for anti-malignant

Language: Английский

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Tumor microbiome – an integral part of the tumor microenvironment

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Nov. 24, 2022

The tumor microenvironment (TME) plays a significant role in progression and cancer cell survival. Besides malignant cells non-malignant components, including immune cells, elements of the extracellular matrix, stromal endothelial microbiome is considered to be an integral part TME. Mounting evidence from preclinical clinical studies evaluated presence type-specific intratumoral bacteria. Differences composition between cancerous tissues benign controls suggest importance microbiome-based approach. Complex host-microbiota crosstalk within TME affects biology via regulation oncogenic pathways, response modulation, interaction with microbiota-derived metabolites. Significantly, involvement tumor-associated microbiota drug metabolism highlights therapeutic implications. This review aims summarize current knowledge about emerging various types solid malignancies. utility treatment also discussed. Moreover, we provide overview trials evaluating patients. research focusing on communication gut microbiomes may bring new opportunities for targeting increase efficacy improve patient outcomes.

Language: Английский

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The ways Fusobacterium nucleatum translocate to breast tissue and contribute to breast cancer development

Molecular Oral Microbiology, Journal Year: 2024, Volume and Issue: 39(1), P. 1 - 11

Published: Jan. 3, 2024

Abstract Breast cancer is among the most prevalent malignancies in women worldwide. Epidemiological findings suggested that periodontal diseases may be associated with breast cancer, which Fusobacterium nucleatum considered an important cross‐participant. In this work, we comprehensively summarize known mechanisms of how F. translocates to, colonizes mammary tumors, and promotes carcinogenesis. Specifically, to tissue through mammary–intestinal axis, direct nipple contact, hematogenous transmission. Subsequently, takes advantage fusobacterium autotransporter protein 2 colonize uses virulence factors adhesin A lipopolysaccharide promote proliferation. Moreover, upregulated matrix metalloproteinase‐9 induced by does not only trigger inflammatory response but also facilitates tumor‐promoting microenvironment. Aside from pro‐inflammatory effect, engaged tumor immune evasion, achieved action on checkpoint receptors highly expressed T cells, natural killer tumor‐infiltrating lymphocytes. Taking as example, more relevant research studies expand our current knowledge oral microbes affect systemic health. Hopefully, exploring these depth could provide new strategies for safer effective biologic targeted therapies at cancer.

Language: Английский

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The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer

Cancer and Metastasis Reviews, Journal Year: 2021, Volume and Issue: 40(4), P. 1223 - 1249

Published: Dec. 1, 2021

Breast cancer, the most frequent cancer in women, is characterized by pathological changes to microbiome of breast tissue, tumor, gut, and urinary tract. Changes are determined stage, grade, origin (NST/lobular), receptor status tumor. This year 50th anniversary when Hill colleagues first showed that gut can support growth, namely oncobiome reactivate excreted estrogens. The currently available human murine data suggest oncobiosis not a cause but its growth. Furthermore, preexisting dysbiosis predisposition transplantable. breast's cancer's inherent promote growth reactivating estrogens, rearranging cell metabolism, bringing about more inflammatory microenvironment, reducing number tumor-infiltrating lymphocytes. produce cytostatic metabolites, production which decreases or blunts cancer. role tract largely uncharted. Oncobiosis supports invasion, metastasis, recurrence supporting cellular movement, epithelial-to-mesenchymal transition, stem function, diapedesis. Finally, modify pharmacokinetics chemotherapeutic drugs. provides novel leverage on should be exploited for better management disease.

Language: Английский

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The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(4), P. 1560 - 1591

Published: Nov. 15, 2023

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on initiation, metastasis, immunosurveillance prognosis despite in low-biomass. The accumulations microbes, their related components metabolites within tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary comprehensively delineate sophisticated landscapes microbe microenvironment, well functions underlying mechanisms. Herein, this review, we focused fields including heterogeneity intratumor different types tumors, controversial roles intratumoral microbiota, basic microenvironment (

Language: Английский

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Tumor Microenvironment Targeted by Polysaccharides in Cancer Prevention: Expanding Roles of Gut Microbiota and Metabolites

Molecular Nutrition & Food Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

ABSTRACT Since the development of immune checkpoint inhibitors (ICIs), immunotherapy has been widely used as a novel cancer treatment. However, efficacy tumor is largely dependent on microenvironment (TME). The high degree heterogeneity within TME remains major obstacle to acquire satisfactory therapeutic. Emerging studies suggest that gut microbiota becoming an important regulator TME. Polysaccharides immunotherapeutic agents or adjuvants not only exhibit antitumor activity by targeting microbiota, but also expand their role in remodeling To date, mechanism which polysaccharides for prevention via deeply investigated. In this review, recent advances regulation through were systematically outlined, and challenges possible solutions clinical application TME‐targeted discussed. Exploring relationship between from perspective may provide new ideas immunotherapy. This area with deserve further exploration.

Language: Английский

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Bacterial metabolites: Effects on the development of breast cancer and therapeutic efficacy (Review)

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(4), P. 1 - 9

Published: March 4, 2025

Evidence suggests that various gut metabolites significantly impact breast cancer (BC) and its treatment. However, the underlying mechanisms remain poorly understood require further investigation. In present study, current literature was reviewed to evaluate roles of microbial in development BC response Microbial metabolites, including secondary bile acids, short‑chain fatty amino acid lipopolysaccharide, nisin pyocyanin, serve crucial microenvironment. promote invasion, metastasis recurrence by facilitating cellular movement, epithelial‑mesenchymal transition, stem cell function diapedesis. Furthermore, certain such as trimethylamine N‑oxide L‑norvaline, can alter pharmacokinetics chemotherapeutic drugs. The review highlights possible involvement bacteriocins carcinogenesis, metastasis. These could provide new insights for treatment strategies are considered potential therapeutic targets.

Language: Английский

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Integrated spatial multi‐omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Abstract Tumour‐associated microbiota are integral components of the tumour microenvironment (TME). However, previous studies on intratumoral primarily rely bulk tissue analysis, which may obscure their spatial distribution and localized effects. In this study, we applied in situ spatial‐profiling technology to investigate breast cancer interactions with local TME. Using 5R 16S rRNA gene sequencing RNAscope FISH/CISH patients’ tissue, identified significant heterogeneity microbiota, Fusobacterium nucleatum ( F. ) predominantly cell‐rich areas. GeoMx digital profiling (DSP) revealed that regions colonized by exhibit influence expression RNAs proteins involved proliferation, migration invasion. vitro indicated co‐culture significantly stimulates proliferation cells. Integrative multi‐omics transcriptomic analyses highlighted MAPK signalling pathways as key altered pathways. By intersecting these datasets, VEGFD PAK1 emerged critical upregulated ‐positive regions, showing strong positive correlations pathway proteins. Moreover, upregulation was confirmed experiments, knockdown reduced ‐induced migration. conclusion, heterogeneity, colonization markedly altering cell protein promote progression These findings provide novel perspectives role cancer, identify potential therapeutic targets, lay foundation for future treatments. Key points Intratumoral exhibits within tissues. alters The is a mediator targets mitigate progression.

Language: Английский

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Multilevel Mechanisms of Cancer Drug Resistance

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12402 - 12402

Published: Nov. 19, 2024

Cancer drug resistance represents one of the most significant challenges in oncology and manifests through multiple interconnected molecular cellular mechanisms. Objective: To provide a comprehensive analysis multilevel processes driving treatment by integrating recent advances understanding genetic, epigenetic, microenvironmental factors. This is systematic review literature focusing on mechanisms cancer resistance, including genomic studies, clinical trials, experimental research. Key findings include following: (1) Up to 63% somatic mutations can be heterogeneous within individual tumors, contributing development; (2) stem cells demonstrate enhanced DNA repair capacity altered metabolic profiles; (3) tumor microenvironment, cancer-associated fibroblasts immune cell populations, plays crucial role promoting resistance; (4) selective pressure from radiotherapy drives emergence radioresistant phenotypes adaptive Understanding complex interplay between various essential for developing effective strategies. Future therapeutic approaches should focus combination strategies that target pathways simultaneously, guided specific biomarkers.

Language: Английский

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The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells

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

Published: Nov. 23, 2023

Introduction Many well-known risk factors for breast cancer are associated with dysbiosis (an aberrant microbiome). However, how bacterial products modulate poorly understood. In this study, we investigated the effect of an exopolysaccharide (EPS) produced by commensal bacterium Bacillus subtilis on phenotypes. Although B. is commonly included in probiotic preparations and its EPS protects against inflammatory diseases, it was virtually unknown whether -derived affects cancer. Methods This work effects phenotypes cells as a model. The proliferation, mammosphere formation, cell migration, tumor growth two immune compromised mouse models. RNA sequencing performed from four treated PBS or EPS. IKKβ STAT1 signaling assessed using pharmacologic RNAi-mediated knock down approaches. Results Short-term treatment inhibited proliferation certain (T47D, MDA-MB-468, HCC1428, MDA-MB-453) while having little others (MCF-7, MDA-MB-231, BT549, ZR-75-30). induced G1/G0 cycle arrest T47D increasing apoptosis MDA-MB-468 cells. also enhanced aggressive including migration stem survival. Long-term (months) led to resistance vitro promoted immunocompromised mice. RNA-sequence analysis showed that increased expression pro-inflammatory pathways NF-κB. and/or necessary sensitive Discussion These results demonstrate multifaceted role molecule secreted warrant future studies competent mice different models fully understand potential benefits side long-term use probiotics.

Language: Английский

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