Secretomes From Non‐Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial‐to‐Mesenchymal Transition DOI Creative Commons

Clara Bourreau,

E. Navarro,

Marine Cotinat

и другие.

Cancer Medicine, Год журнала: 2025, Номер 14(5)

Опубликована: Март 1, 2025

The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and involved in tumorigenesis resistance to therapy. Among the cells TME, endothelial are associated with latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, (ECs) progressively lose their phenotype favor a mesenchymal phenotype, which favors production cancer-associated fibroblasts (CAFs). Our study aimed investigate consequences exposure different secretomes on EC plasticity. Conditioned media (CM) were prepared from lines A549, H1755, H23, H1437, H1975. Proliferation migration ECs treated these CMs assessed by Cyquant Incucyte technologies, respectively. angiogenic capacity was following tubulogenesis Matrigel. Phenotypic changes detected flow cytometry. Morphological analysis actin fibers performed immunohistochemistry, while proteomic mass spectrometry used identify protein content secretomes. A change found when human umbilical vein (HUVECs) CMs. This phenotypic morphological change, an increase both stress fiber expression spontaneous migration. Furthermore, markers (α-SMA CD44) confirmed changes. However, did not modify rate double-labeled (vWF+/α-SMA+ or CD31+/CD44+). Proteomic identified potential targets EndMT therapeutic relevance. Taken together, data suggest that can induce partial EndMT.

Язык: Английский

The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity DOI
Ibrahim AlZaim, Laura de Rooij, Bilal N. Sheikh

и другие.

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(12), С. 691 - 707

Опубликована: Сен. 25, 2023

Язык: Английский

Процитировано

44
Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities DOI

Chad Stroope,

Felix Sebastian Nettersheim, Brian G. Coon

и другие.

Nature Metabolism, Год журнала: 2024, Номер 6(4), С. 617 - 638

Опубликована: Март 26, 2024

Язык: Английский

Процитировано

21
Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies DOI Creative Commons

Nanlin You,

Guohao Liu, Mengchen Yu

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The modification of endothelial cells (ECs) biological function under pathogenic conditions leads to the expression mesenchymal stromal (MSCs) markers, defined as endothelial-to-mesenchymal transition (EndMT). Invisible in onset and slow progression, atherosclerosis (AS) is a potential contributor various atherosclerotic cardiovascular diseases (ASCVD). By triggering AS, EndMT, "initiator" induces progression ASCVD such coronary heart disease (CHD) ischemic cerebrovascular (ICD), with serious clinical complications myocardial infarction (MI) stroke. In-depth research pathomechanisms EndMT identification targeted therapeutic strategies hold considerable value for prevention treatment ASCVD-associated delayed EndMT. Although previous studies have progressively unraveled complexity its pathogenicity triggered by alterations vascular microenvironmental factors, systematic descriptions most recent roles strategies, their future directions are scarce.

Язык: Английский

Процитировано

2
Broadening horizons: molecular mechanisms and disease implications of endothelial-to-mesenchymal transition DOI Creative Commons
Cheng Qian, Guanglu Dong, Chunmei Yang

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 9, 2025

Endothelial-mesenchymal transition (EndMT) is defined as an important process of cellular differentiation by which endothelial cells (ECs) are prone to lose their characteristics and transform into mesenchymal cells. During EndMT, reduced expression adhesion molecules disrupts intercellular adhesion, triggering cytoskeletal reorganization transition. Numerous studies have proved that EndMT a multifaceted biological event driven primarily cytokines such TGF-β, TNF-α, IL-1β, alongside signaling pathways like WNT, Smad, MEK-ERK, Notch. Nevertheless, the exact roles in complicated diseases not been comprehensively reviewed. In this review, we summarize predominant molecular regulatory mechanisms contribute development well highlight contributions series imperative non-coding RNAs curbing initiation EndMT. Furthermore, discuss significant impact on worsening vasculature-related diseases, including cancer, cardiovascular atherosclerosis, pulmonary vascular diabetes-associated fibrotic conditions, cerebral cavernous malformation, providing implications targeting holds promise therapeutic strategy mitigate disease progression.

Язык: Английский

Процитировано

2
Zn-DHM nanozymes regulate metabolic and immune homeostasis for early diabetic wound therapy DOI
Shuo Zhang, Xinyu Zhao, Wei Zhang

и другие.

Bioactive Materials, Год журнала: 2025, Номер 49, С. 63 - 84

Опубликована: Март 6, 2025

Язык: Английский

Процитировано

2
Microenvironmental determinants of endothelial cell heterogeneity DOI

Jesús M. Gómez-Salinero,

David Redmond, Shahin Rafii

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Язык: Английский

Процитировано

1
PD-1 inhibition disrupts collagen homeostasis and aggravates cardiac dysfunction through endothelial-fibroblast crosstalk and EndMT DOI Creative Commons
Zejin Zhang, Zhenzhen Yan, Tao Yuan

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Cardiac immune-related adverse events (irAEs) from PD-1-targeting immune check-point inhibitors (ICIs) are an increasing concern due to their high mortality rate. Collagen plays a crucial role in maintaining cardiac structure, elasticity, and signal transduction; however, the effects mechanisms of PD-1 inhibitor on collagen remodeling remain poorly understood. C57BL/6 mice were injected with anti-mouse antibody create inhibitor-treated model. function was measured by echocardiography, distribution analyzed Masson's trichrome staining Sirius Red staining. Single-nucleus RNA sequencing performed examine inhibition gene expression fibroblasts (CFs) endothelial cells (ECs). EC-CF crosstalk assessed using co-culture experiments ELISA. ChIP assay analyze regulation TCF12 TGF-β1 promoter. Western blot, qRT-PCR, immunofluorescence used detect TCF12, TGF-β1, endothelial-to-mesenchymal transition (EndMT) markers. Reactive oxygen species (ROS) levels evaluated DHE staining, MDA content, SOD activity assays. We report newly discovered cardiotoxic effect inhibitor, which causes aberrant heart, marked decrease interstitial increase perivascular deposition. Mechanistically, does not directly affect CFs but instead impact them through crosstalk. reduces secretion ECs downregulating we identify as transcriptional promoter TGF-β1. This subsequently decreases CF activity, leading reduced Additionally, induces EndMT, The dysfunction induced results ROS accumulation ECs. Inhibiting N-acetylcysteine (NAC) preserves normal reversing downregulation EndMT Our suggest that ECs, imbalanced (decrease collagen) heart modulating TCF12/TGF-β1-mediated EndMT. NAC supplementation could be effective clinical strategy mitigate inhibitor-induced dysfunction.

Язык: Английский

Процитировано

1
GPER1/ACACB are potential target genes associated with intracranial aneurysm and vascular endothelial cell senescence DOI
Lang Zeng, Xuanzhen Lu, Yuzhen Huang

и другие.

Neurosurgical Review, Год журнала: 2025, Номер 48(1)

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

1
Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology DOI Open Access
Aman Singh,

Kriti Bhatt,

Hien C. Nguyen

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6180 - 6180

Опубликована: Июнь 4, 2024

Under different pathophysiological conditions, endothelial cells lose phenotype and gain mesenchymal cell-like via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, expression of cell-specific markers such CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, vascular-endothelial cadherin α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, collagens. EndMT is induced by numerous pathways triggered modulated multiple often redundant mechanisms in context-dependent manner depending on status cell. plays an essential role embryonic development, particularly atrioventricular valve development; however, also implicated pathogenesis several genetically determined acquired diseases, including malignant, cardiovascular, inflammatory, fibrotic disorders. Among cardiovascular aberrant reported atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, cardiac fibrosis. Accordingly, understanding behind cause and/or effect to eventually target appears be promising strategy for treating EndMT-associated diseases. However, this approach limited lack precise functional pathways, causes effects, robust animal models human data about Here, we review various

Язык: Английский

Процитировано

6
The influence of endothelial metabolic reprogramming on the tumor microenvironment DOI Creative Commons

Kelby M. Kane,

Deanna N. Edwards, Jin Chen

и другие.

Oncogene, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Abstract Endothelial cells (ECs) that line blood vessels act as gatekeepers and shape the metabolic environment of every organ system. In normal conditions, endothelial are relatively quiescent with organ-specific expression signatures profiles. cancer, ECs metabolically reprogrammed to promote formation new fuel tumor growth metastasis. addition EC’s role on cells, tortuous vasculature contributes an immunosuppressive by limiting T lymphocyte infiltration activity while also promoting recruitment other accessory pro-angiogenic immune cells. These elements aid in metastatic spreading cancer contribute therapeutic resistance. The concept restoring a more stabilized concert immunotherapy is emerging potential approach overcoming barriers treatment. This review summarizes metabolism their regulation nutrient uptake delivery, impact shaping microenvironment anti-tumor immunity. We highlight approaches target harness response. Appreciating integration state levels crosstalk among TME may provide avenues for intervention.

Язык: Английский

Процитировано

5