Mapping Tumor–Stroma–ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer DOI Creative Commons

A.C. Kataki,

Priyanka Gupta, Umber Cheema

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Bioengineering-based in vitro tumor models are increasingly important as tools for studying disease progression and therapy response many cancers, including the deadly pancreatic ductal adenocarcinoma (PDAC) that exhibits a tumor/tissue microenvironment of high cellular/biochemical complexity. Therefore, it is crucial to capture complexity enable investigation interplay between cancer cells factors such extracellular matrix (ECM) proteins or stroma cells. Using polyurethane (PU) scaffolds, we performed systematic study on how different ECM protein scaffold coatings impact long-term cell evolution scaffolds containing only (activated stellate endothelial cells). To investigate potential further changes those biomarkers due cancer-stroma interactions, mapped their expression dual/zonal consisting core periphery, spatially mimicking fibrotic/desmoplastic reaction PDAC. In our single observed coating affected spatial aggregation, deposition, biomarker upregulation cell-line-dependent manner. levels fibrosis/desmoplasia terms composition/quantity were generated depending coating. When model, linked aggressiveness/invasiveness upregulated by both compared models. Collectively, advances understanding PU scaffolds. Our findings show within bioengineered models, can stimulate PDAC develop aggressiveness/invasiveness, well fibrosis. Furthermore, highlight importance considering map invasion. work contributes design with variable, yet biomimetic, tissue-like properties microenvironment's role progression.

Язык: Английский

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Язык: Английский

Процитировано

26
Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis DOI
Hardeep Singh Tuli, Jagjit Kaur,

Kanupriya Vashishth

и другие.

Archives of Toxicology, Год журнала: 2022, Номер 97(1), С. 103 - 120

Опубликована: Ноя. 28, 2022

Язык: Английский

Процитировано

57
Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment DOI Open Access
Kena Song,

Zhangqing Yu,

Xiangyang Zu

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10509 - 10509

Опубликована: Сен. 10, 2022

The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of ECM, are greatly remodeled alongside development. More and more studies have confirmed that collagens changed from barrier to providing assistance In this course, cause remodeling progression, which turn, promotes interaction between tumor cells complex with biochemical mechanical signals intervention through activating diverse signal pathways. As mechanism gradually clears, it becomes new target find opportunities diagnose treat cancer. review, we investigated process collagen progression discussed cells. Several typical effects associated were highlighted such fibrillation precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, guiding invasion. Then, values diagnosis prognosis focused on. It worth noting several generated fragments serum reported be able biomarkers for prognosis, beneficial clinic detection. At glance, variety summarized. Many collagen-associated targets drugs been treatment recent years. related review. mass data collected classified by mechanism. Overall, complicated, mechanisms not completely clear. A lot excavated diagnosis. However, therapeutic almost clinical trials, merely few applications. So, efforts needed collagens-associated drug development research treatment.

Язык: Английский

Процитировано

53
The prognostic value and molecular properties of tertiary lymphoid structures in oesophageal squamous cell carcinoma DOI Creative Commons

Yihong Ling,

Jian Zhong,

Zelin Weng

и другие.

Clinical and Translational Medicine, Год журнала: 2022, Номер 12(10)

Опубликована: Окт. 1, 2022

Tertiary lymphoid structures (TLSs) play key roles in tumour adaptive immunity. However, the prognostic value and molecular properties of TLSs oesophageal squamous cell carcinoma (ESCC) patients have not been studied.The values presence maturation status tumour-associated were determined 394 256 ESCC from Sun Yat-sen University Cancer Center (Centre A) Hospital Shantou Medical College B), respectively. A deep-learning (DL) TLS classifier was established with haematoxylin eosin (H&E)-stained slides using an inception-resnet-v2 neural network. Digital spatial profiling performed to determine cellular tissues.TLSs observed 73.1% ESCCs Centre via pathological examination H&E-stained primary slides, among which 42.9% TLS-mature 30.2% TLS-immature tumours. The DL yielded favourable sensitivities specificities for patient identification evaluation, 55.1%, 39.5% 5.5% B identified as TLS-mature, TLS-negative Multivariate analyses proved that mature independent factor both cohorts (p < .05). Increased proportions proliferative B, plasma CD4+ T helper (Th) cells increased memory Th17 signatures compared immature ones. Intratumoural CD8+ infiltration tissues TLS-absent tissues. combination high associated best survival patients.Mature improve prognosis who underwent complete resection. use would facilitate precise efficient evaluation offer a novel probability treatment individualization.

Язык: Английский

Процитировано

51
Morphometry and mechanical instability at the onset of epithelial bladder cancer DOI Creative Commons
Franziska L. Lampart, Roman Vetter, Kevin A. Yamauchi

и другие.

Nature Physics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Abstract Malignancies of epithelial tissues, called carcinomas, account for most cancer cases. Research has largely focused on correlating different carcinoma subtypes to genetic alterations. However, as well a rewiring in the signalling networks, progression is accompanied by mechanical changes cells and extracellular matrix. Here we reveal intricate morphologies basement membrane at onset bladder propose that they emerge from instability upon overgrowth. We imaged mouse human tissue performed differential growth simulations, found stiffness mucosa layers can result aberrant morphologies. The resulting thickening, wrinkles folds resemble early papillary tumours carcinomas situ. Atomic force microscopy confirmed local pathological membrane. Our findings suggest possible origin may guide future developments treatment prophylaxis.

Язык: Английский

Процитировано

1
Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration DOI Creative Commons
W. H. Tian,

Yongzhou Luo,

Yuhui Tang

и другие.

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(5), С. 1645 - 1663

Опубликована: Янв. 1, 2023

Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance.Nevertheless, an efficacious prognostic signature for recognizing this population lacking.The basement membrane (BM) has been proven be strongly involved progression metastasis, the potential a powerful predictor cancer.In study, substantial bulk RNA transcriptomics, single cell transcriptomics clinical information were collected from TCGA-BRCA, METABRIC GSE96058, Kaplan-Meier survival curves, analysis vitro experiments conducted validate signature.From results, index, namely, BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 PXDNL.Verification by independent cohorts showed that high BMscore had distinctly worse outcome.By integrating factors, we constructed nomogram displayed good predictive capability.Furthermore, evaluated implication of immune infiltration.More importantly, positive correlation between EMT activity revealed immunohistochemistry experiments.Taken together, provided novel gene predict prognosis metastasis accurately, which may help individualized decision-making.

Язык: Английский

Процитировано

21
Genetic susceptibility to prostate cancer in Taiwan: A genome‐wide association study DOI
Da‐Tian Bau, Chia‐Wen Tsai,

WEN-SHIN CHANG

и другие.

Molecular Carcinogenesis, Год журнала: 2024, Номер 63(4), С. 617 - 628

Опубликована: Фев. 23, 2024

Abstract We conducted the first genome‐wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single‐nucleotide polymorphisms (SNPs) reached significance ( p < 5 × 10 −8 ). Among these, three were distinct from previously identified loci: rs76072851 CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36–1.76, 5.30 −11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 PCAT2 (8q24.21), OR 1.41 (95% CI, 1.31–1.51), 8.77 −21 rs56339048, an lncRNA gene, CASC8 1.25 1.16–1.35), 2.14 . refined lead SNPs for Taiwanese: rs13255059 (near ), 9.02 −43 , rs1456315 (inside 4.33 −42 confirmed 35 out 49 GWAS‐identified East Asian PCa susceptibility SNPs. In addition, we more specific to Taiwanese than Asians: rs34295433 LAMC1 (1q25.3) rs6853490 PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using 40 validated area under receiver‐operating characteristic curve GRS predict 0.67 0.63–0.71). These provide valuable insights into molecular mechanisms carcinogenesis underscore significant role regional differences incidence.

Язык: Английский

Процитировано

9
Integrating integrins with the hallmarks of cancer DOI Creative Commons
Scott M. Haake, Brenda Rios, Ambra Pozzi

и другие.

Matrix Biology, Год журнала: 2024, Номер 130, С. 20 - 35

Опубликована: Апрель 25, 2024

Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them polarize and form epithelial tissues. The provides essential physical scaffolding biochemical biophysical cues required for tissue morphogenesis, differentiation, function, homeostasis. cell adhesion (i.e., membrane) plays critical role in organizing tissues, separating from stroma. detachment classically results death, though or invasion through represents step carcinogenesis. bind via receptors, including integrins. Integrins are transmembrane receptors that mechanical linkage between intracellular cytoskeleton anchorage-dependent cellular functions such as proliferation, migration, invasion. of integrins development, growth, dissemination multiple types carcinomas has been investigated by numerous methodologies, led great complexity. To organize this vast array information, we have utilized "Hallmarks Cancer" Hanahan Weinberg convenient framework discuss pathogenesis cancers. This review explores biology how its complexity impacted development integrin-targeted anti-cancer therapeutics.

Язык: Английский

Процитировано

8
Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis DOI Creative Commons
Yu Liu, Zhenyu Yang, Jingya Jane Pu

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(3)

Опубликована: Март 1, 2025

Oral squamous cell carcinoma (OSCC) is an increasingly prevalent malignancy worldwide. This study aims to understand molecular alterations associated with lymph node metastasis of OSCC in order improve treatment strategies. We analysed a cohort 46 patients primary OSCC, including 10 and 36 without. Using comprehensive multi-omics approach - encompassing genomic, transcriptomic, proteomic, epigenetic, single-cell, spatial analyses we integrated data delineate the landscape context metastasis. Our genomic analysis identified significant mutations key genes within MAPK, TGF-β WNT signalling pathways, which are essential for tumour development. The proteogenomic highlighted pathways critical dissemination factors contributing immunosuppressive microenvironment. Elevated levels POSTN were found reorganise extracellular matrix (ECM), interact TGF-β, disrupt cycle regulation suppress immune response by reducing VCAM1 activity. Integrated single-cell transcriptome revealed that cancer-associated fibroblasts (CAFs) secrete TGF-β1/2, promoting cancer through epithelial-mesenchymal transition (EMT). provides detailed understanding mechanisms driving OSCC. These insights could lead more precise diagnostics targeted treatments. article protected copyright. All rights reserved.

Язык: Английский

Процитировано

1
Forskolin affects proliferation, migration and Paclitaxel-mediated cytotoxicity in non-small-cell lung cancer cell lines via adenylyl cyclase/cAMP axis DOI Creative Commons

Alessia Salzillo,

Angela Ragone,

Annamaria Spina

и другие.

European Journal of Cell Biology, Год журнала: 2023, Номер 102(2), С. 151292 - 151292

Опубликована: Янв. 28, 2023

Non-Small-Cell Lung Cancer (NSCLC) is considered one of the most frequently diagnosed cancers and leading cause cancer-related deaths worldwide. Despite undoubted therapeutic advances that have occurred in clinical practice over time, due to its high degree both heterogeneity resistance, NSCLC remains largely incurable. As a natural cAMP elevating agent, Forskolin has shown anti-cancer properties different tumor types, thus supposing possible usage treating malignancies. In this study, we investigated outcome H1299 A549 cell lines, either alone or combination with Paclitaxel. We proved impairs growth migration ability these cells, concurrently. Albeit extent between A549, changes cell-cycle progression epithelial-mesenchymal markers were observed response administration. Interestingly, comparable impairment was also obtained phosphodiesterase inhibitor IBMX, while employment adenylyl cyclase SQ22536 counteracted, at least part, Forskolin-mediated anticancer effects. Besides as single demonstrated strongly enhances Paclitaxel-induced cytotoxicity, affecting death mainly via apoptosis induction. Notably, H89-mediated protein kinase A (PKA) inhibition further deteriorated outcome. Altogether, our data designate molecule NSCLC, recognize cyclase/cAMP axis pathways involved in. Although achieved preclinical stage, findings encourage design future studies aimed exploring treatment.

Язык: Английский

Процитировано

15