Unveiling immune cell response disparities in human primary cancer-associated fibroblasts between two- and three-dimensional cultures DOI Creative Commons

Jianping Yang,

Nikhil N Kulkarni, Masashi Yamaji

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(12), P. e0314227 - e0314227

Published: Dec. 19, 2024

Cancer-associated fibroblasts (CAFs) play pivotal roles in solid tumor initiation, growth, and immune evasion. However, the optimal biomimetic modeling conditions remain elusive. In this study, we investigated effects of 2D 3D culturing on human primary CAFs integrated into a modular microenvironment (TME). Using single-nucleus RNA sequencing (snRNAseq) Proteomics’ Proximity Extension Assays, characterized CAF transcriptomic profiles cytokine levels. Remarkably, when cultured 2D, exhibited myofibroblast (myCAF) subtype, whereas spheroid cultures, displayed more inflammatory (iCAF) pathological state. By integrating single-cell gene expression data with functional interrogations critical TME-related processes [natural killer (NK)-mediated killing, monocyte migration, macrophage differentiation], were able to reconcile form function. TME models, enhance cancer cell growth immunologically shield cells from NK cell-mediated cytotoxicity, striking contrast their counterparts. Notably, CAF-secreted proteins manifest immunosuppressive profile by enhancing transendothelial migration differentiation M2-like tumor-associated macrophages (TAMs). Our findings reveal clinically relevant desmoplastic model that can be employed industrial drug discovery campaigns expand cellular target range chemotherapeutics.

Language: Английский

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

Alexandra Buruiană,

Bogdan‐Alexandru Gheban,

Ioana‐Andreea Gheban‐Roșca

et al.

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

Citations

7
Engineered nano-aluminum adjuvant for cancer immunotherapy: Progress, challenges and opportunities towards preclinical/clinical application DOI Creative Commons
Chong Gao, Jianping Jiang, Jing Zhao

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 519, P. 216109 - 216109

Published: Aug. 1, 2024

Immunotherapy is a promising strategy to inhibit the progression of solid tumors. However, current vaccine adjuvants represented by aluminum adjuvant (Alum) fail tumor antigens initiate effective T cell immunity. Despite efforts have been made optimize physical characteristics Alum, lack specific immunostimulatory functions still results in their inability effectively induce cytotoxic immune responses. Encouragingly, an iterative layered double hydroxide (LDH) nano‑aluminum (NanoAlum) re-engineered from clinical AlOOH Alum and Mg(OH)2 antacid has shown efficacy evoking both potent humoral cellular Notably, it can also serve as microenvironmental immunomodulator reshape aberrant physicochemical attributes microenvironment. Interestingly, highly flexible crystal structure chemical composition offer variety LDH-based candidates (NanoMAlum) doping with body essential nutritional metal ions (M), which show great potential amplify immunotherapy. In this review, we summarize development progress LDH NanoAlum its variants NanoMAlum for cancer By rethinking challenges that hindered preclinical/clinical application, charted research pathway based on engineered organoids accelerate applications these NanoMAlums review.

Language: Английский

Citations

7
Chromatin plasticity in mechanotransduction DOI Creative Commons
Maria Vivo,

Valentina Rosti,

Sara Cervone

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102376 - 102376

Published: May 28, 2024

Living organisms can detect and respond to physical forces at the cellular level. The pathways that transmit these nucleus allow cells react quickly consistently environmental changes. Mechanobiology involves interaction between biological processes is crucial for driving embryonic development adapting cues during adulthood. Molecular studies have shown sense mechanical signals directly through membrane receptors linked cytoskeleton or indirectly biochemical cascades influence gene expression adaptation. This review will explore role of epigenetic modifications, emphasizing 3D genome architecture nuclear structures as responders stimuli, which ensure memory adaptability. Understanding how are transduced regulate cell functioning, governing such programming reprogramming, essential advancing our knowledge human diseases.

Language: Английский

Citations

5
Platycodin D inhibits tumor proliferation by modulating macrophage polarization through promoting JAK2 ubiquitination DOI
Wei Wu, Jie Zhang, Z Wang

et al.

Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 125, P. 106671 - 106671

Published: Jan. 18, 2025

Language: Английский

Citations

0
Intrinsic bioenergetic adaptations compensate for reduced mitochondrial content in HER2-driven mammary tumors DOI Open Access
Sara M. Frangos, Henver S. Brunetta, Dongdong Wang

et al.

Published: Feb. 7, 2025

It is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target respiration with inhibitors oxidative phosphorylation highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed bulk and metabolic phenotype murine HER2-driven mammary tumors paired benign tissue. Transcriptomic proteomic profiling revealed are characterized by downregulation genes/proteins compared tissue, including general OXPHOS subunits comprising Complexes I-IV. Despite this observation, supported both carbohydrate-derived substrates (pyruvate) lipids (palmitoyl-carnitine) was several-fold higher which persisted regardless normalization method (i.e. wet weight, total protein content when corrected content). This upregulated respiratory capacity could not be explained uncoupling; several subunits/regulators Complex V function were downregulated tumors, suggesting possible compensatory effects may contribute high rates. Furthermore, displayed smaller more punctate morphology, aligning reduction fusion increase fission markers, improved efficiency. Together, data highlights typical correlation apply all types implicates activation supporting tumorigenesis model.

Language: Английский

Citations

0
Intrinsic bioenergetic adaptations compensate for reduced mitochondrial content in HER2-driven mammary tumors DOI Open Access
Sara M. Frangos, Henver S. Brunetta, Dongdong Wang

et al.

Published: Feb. 7, 2025

It is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target respiration with inhibitors oxidative phosphorylation highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed bulk and metabolic phenotype murine HER2-driven mammary tumors paired benign tissue. Transcriptomic proteomic profiling revealed are characterized by downregulation genes/proteins compared tissue, including general OXPHOS subunits comprising Complexes I-IV. Despite this observation, supported both carbohydrate-derived substrates (pyruvate) lipids (palmitoyl-carnitine) was several-fold higher which persisted regardless normalization method (i.e. wet weight, total protein content when corrected content). This upregulated respiratory capacity could not be explained uncoupling; several subunits/regulators Complex V function were downregulated tumors, suggesting possible compensatory effects may contribute high rates. Furthermore, displayed smaller more punctate morphology, aligning reduction fusion increase fission markers, improved efficiency. Together, data highlights typical correlation apply all types implicates activation supporting tumorigenesis model.

Language: Английский

Citations

0
Tumor-on-chip platforms for breast cancer continuum concept modeling DOI Creative Commons

Anca-Narcisa Neagu,

Danielle Whitham, Pathea Bruno

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 2, 2024

Our previous article entitled "Proteomics and its applications in breast cancer", proposed a Breast Cancer Continuum Concept (BCCC), including Cell as well Proteomic Concept. cancer-on-chip (BCoC), cancer liquid biopsy-on-chip (BCLBoC), metastasis-on-chip (BCMoC) models successfully recapitulate reproduce

Language: Английский

Citations

1
Cancer Patient-Derived Cell-Based Models: Applications and Challenges in Functional Precision Medicine DOI Creative Commons
Jelena Dinić, Sofija Jovanović Stojanov, Miodrag Dragoj

et al.

Life, Journal Year: 2024, Volume and Issue: 14(9), P. 1142 - 1142

Published: Sept. 10, 2024

The field of oncology has witnessed remarkable progress in personalized cancer therapy. Functional precision medicine emerged as a promising avenue for achieving superior treatment outcomes by integrating omics profiling and sensitivity testing patient-derived cells. This review paper provides an in-depth analysis the evolution cancer-directed drugs, resistance mechanisms, role functional platforms revolutionizing individualized strategies. Using two-dimensional (2D) three-dimensional (3D) cell cultures, xenograft (PDX) models, advanced assays significantly improved our understanding tumor behavior drug response. will lead to identifying more effective treatments patients. Considering limited eligibility patients based on genome-targeted approach receiving targeted therapy, unprecedented opportunities customizing medical interventions according individual patient traits responses. delineates current landscape, explores limitations, presents future perspectives inspire ongoing advancements

Language: Английский

Citations

0
Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Platycodonis radix inhibits tumor DOI Creative Commons
Wei Wu, Chuan Cheng, Z Wang

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 121, P. 106458 - 106458

Published: Sept. 13, 2024

Language: Английский

Citations

0
Intrinsic bioenergetic adaptations compensate for reduced mitochondrial content in HER2-driven mammary tumors DOI Creative Commons
Sara M. Frangos, Henver S. Brunetta, Dongdong Wang

et al.

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

Published: Nov. 3, 2024

ABSTRACT It is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target respiration with inhibitors oxidative phosphorylation highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed bulk and metabolic phenotype murine HER2-driven mammary tumors paired benign tissue. Transcriptomic proteomic profiling revealed are characterized by downregulation genes/proteins compared tissue, including general OXPHOS subunits comprising Complexes I-IV. Despite this observation, supported both carbohydrate-derived substrates (pyruvate) lipids (palmitoyl-carnitine) was several-fold higher which persisted regardless normalization method (i.e. wet weight, total protein content when corrected content). This upregulated respiratory capacity could not be explained uncoupling; several subunits/regulators Complex V function were downregulated tumors, suggesting possible compensatory effects may contribute high rates. Furthermore, displayed smaller more punctate morphology, aligning reduction fusion increase fission markers, improved efficiency. Together, data highlights typical correlation apply all types implicates activation supporting tumorigenesis model.

Language: Английский

Citations

0