Endothelial cell dysfunction in cancer: a not-so-innocent bystander DOI Creative Commons
Betül Ünlü, Neha Joshi, Jamie M. O’Sullivan

и другие.

Bleeding Thrombosis and Vascular Biology, Год журнала: 2024, Номер 3(s1)

Опубликована: Май 16, 2024

The body’s homeostasis depends on the vascular endothelium, which controls angiogenesis, tone, inflammation, cell trafficking, hemostasis, and movement of nutrients waste out body. Endothelial cells (ECs) are primary gatekeepers many these vessel wall functions, despite only having a single cell’s thickness. Normally quiescent ECs in context cancer activated by anti-cancer therapies, tumor microenvironment, factors secreted tumor. Crucially, this dysfunctional endothelium actively participates metastasis progression rather than just acting as passive bystander. Compared to healthy vasculature, vasculature heterogeneous have different gene expression profile. Tumor-associated ECs, particular, exhibit increased pro-angiogenic characteristics upregulated adhesion molecules proinflammatory cytokines, facilitating intra- extravasation spreading cells. Furthermore, downregulation important anticoagulant endothelial secretion prothrombotic can directly encourage cancer-associated thrombosis. Many therapies also less effective their delivery function when there is dysfunction endothelium. review highlights some most recent research showing how tumor-associated influence coagulation, contribute tumors. Undoubtedly, better understanding microenvironment subverts phenotypic alterations support survival spread will aid identification new therapeutic targets slow advancement cancer.

Язык: Английский

Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism DOI Creative Commons
Fan Yang,

Gloria Lee,

Yi Fan

и другие.

Angiogenesis, Год журнала: 2024, Номер 27(3), С. 333 - 349

Опубликована: Апрель 6, 2024

Abstract Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, facilitates immune evasion. Therapeutic strategies targeting vasculature have emerged transformative for treatment, encompassing anti-angiogenesis, vessel normalization, endothelial reprogramming. Growing evidence suggests the dynamic regulation by infiltrating myeloid cells, such macrophages, myeloid-derived suppressor cells (MDSCs), neutrophils. Understanding these regulatory mechanisms is pivotal in paving way successful vasculature-targeted treatments. interventions aimed to disrupt cell-mediated may reshape overcome resistance radio/chemotherapy immunotherapy.

Язык: Английский

Процитировано

24
Single-cell analyses reveal evolution mimicry during the specification of breast cancer subtype DOI Creative Commons

Zhijie Gao,

Huan Fang,

Si Sun

и другие.

Theranostics, Год журнала: 2024, Номер 14(8), С. 3104 - 3126

Опубликована: Янв. 1, 2024

Background:The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic epigenetic programs.A comprehensive characterization mapping of the cell-of-origin breast using novel technologies unveil subtype-specific therapeutic targets is still absent.Methods: We integrated 195,144 high-quality from normal tissues 406,501 primary samples create a large-scale single-cell atlas human cancerous breasts.Potential heterogeneous origin malignant was explored by contrasting against reference epithelial cells.Multi-omics analyses both in vitro vivo experiments were performed screen validate potential treatment targets.Novel biomarkers identified immune stromal subpopulations validated immunohistochemistry our cohort.Results: Tumor stratification based on patterns correlated with clinical outcomes, genomic aberrations diverse microenvironment constitutions.We found that luminal (LP) subtype robustly associated poor prognosis, instability dysfunctional microenvironment.However, LP patients sensitive neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) immunotherapy.The target PLK1 investigated experiments.Besides, profiling inspired us identify range clinically relevant subpopulations, including subsets innate lymphoid (ILCs), macrophages endothelial cells. Conclusion:The present study revealed cellular repertoire cancer.Combining bulk transcriptome data, we elucidated evolution mimicry subtypes expounded vital implications.Novel could be targets.Taken together, Our findings lay foundation for precise prognostic cancer.

Язык: Английский

Процитировано

8
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers DOI Creative Commons
Jinhu Li, Dongfang Wang, Fei Tang

и другие.

National Science Review, Год журнала: 2024, Номер 11(9)

Опубликована: Июль 10, 2024

ABSTRACT Therapeutics targeting tumor endothelial cells (TECs) have been explored for decades, with only suboptimal efficacy achieved, partly due to an insufficient understanding of the TEC heterogeneity across cancer patients. We integrated single-cell RNA-seq data 575 patients from 19 solid types, comprehensively charting phenotypic diversities. Our analyses uncovered underappreciated compositional and functional in TECs a pan-cancer perspective. Two subsets, CXCR4+ tip SELE+ veins, represented prominent angiogenic proinflammatory phenotypes TECs, respectively. They exhibited distinct spatial organization patterns, compared adjacent non-tumor tissues, tissue showed increased prevalence cells, yet veins depleted. Such characteristics underlie their differential associations response anti-angiogenic therapies immunotherapies. integrative resources findings open new avenues understand clinically intervene vasculature.

Язык: Английский

Процитировано

8
Clinical Potential of YY1-Hypoxia Axis for Vascular Normalization and to Improve Immunotherapy DOI Open Access

Concetta Meo,

Filomena de Nigris

Cancers, Год журнала: 2024, Номер 16(3), С. 491 - 491

Опубликована: Янв. 23, 2024

Abnormal vasculature in solid tumors causes poor blood perfusion, hypoxia, low pH, and immune evasion. It also shapes the tumor microenvironment affects response to immunotherapy. The combination of antiangiogenic therapy immunotherapy has emerged as a promising approach normalize unlock full potential However, unpredictable redundant mechanisms vascularization suppression triggered by tumor-specific hypoxic microenvironments indicate that such therapies need be further evaluated improve patient outcomes. Here, we provide an overview interplay between angiogenesis modulation review function mechanism YY1-HIF axis regulates vascular microenvironment. Furthermore, discuss targeting YY1 other strategies, nanocarrier delivery systems engineered cells (CAR-T), re-establish immune-permissive enhance efficacy cancer therapy.

Язык: Английский

Процитировано

4
ITGA4 as a potential prognostic and immunotherapeutic biomarker in human cancer and its clinical significance in gastric cancer: an integrated analysis and validation DOI Creative Commons
Jiaxing Zhang, Gang Wang, Jie Liu

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 12, 2025

Background Integrin Subunit Alpha 4 (ITGA4), a member of the integrin protein family, is involved in progression malignant tumors. However, its role across different cancer types not well understood. Methods Utilizing multi-omics data, we comprehensively evaluated ITGA4’s expression, clinical relevance, diagnostic and prognostic value, functions, mutations, methylation status, along with impact on immunity, mismatch repair (MMR), heterogeneity, stemness, immunotherapy responsiveness, drug resistance pan-cancer, partial validation gastric (GC) using transcriptomic analysis, single-cell western blot (WB), wound-healing assay, flow cytometry immunohistochemistry (IHC). We further investigated correlation clinicopathology serological markers tissues from 80 GC patients. Results ITGA4 expression was generally low normal but varied significantly tumor types, higher levels advanced stages grades. It demonstrated value 20 effectively predicted 1-, 3-, 5-year survival rates as part model. played roles cell adhesion, migration, immune regulation, pathways like PI3K-Akt TSC-mTOR. showed alterations 22 at 9 sites inhibiting expression. positively correlated infiltration, regulatory genes, chemokines, might reduce microsatellite instability (MSI) mutation burden (TMB) by promoting MMR gene could also predict efficacy chemotherapy sensitivity. In GC, high related to poor prognosis, promoted proliferation enhanced infiltration. cells than ones. Its downregulation inhibited migration apoptosis. Moreover, N stage, pathological neural vascular invasion, serum Ki-67, cells, CRP CA125. Conclusion potential biomarker therapeutic target enhance treatment improve patient outcomes.

Язык: Английский

Процитировано

0
The vascular microenvironment and its stem cells regulate vascular homeostasis DOI Creative Commons
Yanhui Wang, Xiaoyun Zhang, Xin Li

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

The vascular microenvironment comprises of anatomical structures, extracellular matrix components, and various cell populations, which play a crucial role in regulating homeostasis influencing structure function. Under physiological conditions, intrinsic regulation the is required to sustain homeostasis. In contrast, under pathological alterations this lead injury remodeling. According anatomy, can be subdivided into three sections from inside out. endothelial microenvironment, centered on cells (VECs), includes physicochemical factors. VECs interact with factors regulate function parenchymal cells, including hepatocytes, neurons tumor cells. wall comprising vasa vasorum their unique stem/progenitor niches, plays pivotal inflammation Additionally, perivascular adipose tissue, consists adipocytes stem contribute processes atherosclerosis. It anticipated that targeted will emerge as novel approach for treatment diseases. Accordingly, review examine by cardiovascular

Язык: Английский

Процитировано

0
Immunomodulatory Therapy for Ischemic Heart Disease DOI

X. Zhao,

Thomas Williamson, Yanqing Gong

и другие.

Circulation, Год журнала: 2024, Номер 150(13), С. 1050 - 1058

Опубликована: Сен. 23, 2024

Ischemic heart disease is a leading cause of death worldwide, manifested clinically as myocardial infarction (and ischemic cardiomyopathy. Presently, there exists notable scarcity efficient interventions to restore cardiac function after infarction. Cumulative evidence suggests that impaired tissue immunity within the microenvironment aggravates dysfunction, contributing progressive failure. Recent research breakthroughs propose immunotherapy potential approach by leveraging immune and stroma cells recalibrate microenvironment, holding significant promise for treatment disease. In this Primer, we highlight three emerging strategies immunomodulatory therapy in managing cardiomyopathy: targeting vascular endothelial rewire immunity, reprogramming myeloid bolster their reparative function, utilizing adoptive T cell ameliorate fibrosis. We anticipate will offer exciting opportunities treatment.

Язык: Английский

Процитировано

1
Integrative multi-omics analysis reveals the role of tumor-associated endothelial cells and their signature in prognosis of intrahepatic cholangiocarcinoma DOI Creative Commons

Hao Jiang,

Biao Gao,

Zihe Meng

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Окт. 19, 2024

This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune within tumor microenvironment (TME) its impact on prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients reveal role TECs in angiogenesis their significant heterogeneity. Meanwhile, we identified genes highly expressed constructed TEC signatures (TEC.Sig). Next, calculated scores samples based TEC.Sig. Patients with higher exhibited a frequency KRAS mutations, which was associated increased infiltration neutrophils immature dendritic (iDCs), decreased numbers natural killer (NK), CD4 + T, CD8 T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations CXCL12 overexpression showed contrasting trend. Spatial transcriptomics analysis histological experiments further confirmed that interacted various tumor-killing through CXCL12/CXCR4 axis. Multiple immunotherapy datasets TEC.Sig could predict patient responses immunotherapy. The score is promising reliable biomarker for predicting genetic prognosis ICC patients. Enhancing regulation signaling pathway may represent potential novel therapeutic target treatment.

Язык: Английский

Процитировано

1
Endothelial cell dysfunction in cancer: a not-so-innocent bystander DOI Creative Commons
Betül Ünlü, Neha Joshi, Jamie M. O’Sullivan

и другие.

Bleeding Thrombosis and Vascular Biology, Год журнала: 2024, Номер 3(s1)

Опубликована: Май 16, 2024

The body’s homeostasis depends on the vascular endothelium, which controls angiogenesis, tone, inflammation, cell trafficking, hemostasis, and movement of nutrients waste out body. Endothelial cells (ECs) are primary gatekeepers many these vessel wall functions, despite only having a single cell’s thickness. Normally quiescent ECs in context cancer activated by anti-cancer therapies, tumor microenvironment, factors secreted tumor. Crucially, this dysfunctional endothelium actively participates metastasis progression rather than just acting as passive bystander. Compared to healthy vasculature, vasculature heterogeneous have different gene expression profile. Tumor-associated ECs, particular, exhibit increased pro-angiogenic characteristics upregulated adhesion molecules proinflammatory cytokines, facilitating intra- extravasation spreading cells. Furthermore, downregulation important anticoagulant endothelial secretion prothrombotic can directly encourage cancer-associated thrombosis. Many therapies also less effective their delivery function when there is dysfunction endothelium. review highlights some most recent research showing how tumor-associated influence coagulation, contribute tumors. Undoubtedly, better understanding microenvironment subverts phenotypic alterations support survival spread will aid identification new therapeutic targets slow advancement cancer.

Язык: Английский

Процитировано

0