Tumour associated endothelial cells: origin, characteristics and role in metastasis and anti-angiogenic resistance

Yao, Xinghong; Zeng, Ye

doi:10.3389/fphys.2023.1199225

Cited by 16 publications

(5 citation statements)

References 104 publications

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“…Angiogenesis is supported by dynamic endothelial cell functions, such as proliferation, migration, invasion, and tube formation, which are essential to the formation of vessel sprouts ( 6 , 28 ). In this study, we explored the roles of FHL2 in NSCLC angiogenesis and vascular permeability, as well as its underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability

Chen,

Chen

et al. 2024

J Thorac Dis

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Background Antiangiogenetic therapy is one of the effective strategies for non-small cell lung cancer (NSCLC) treatment. Four-and-a-half LIM-domain protein 2 ( FHL2 ) serves as a key function in cell growth and metastasis of multiple cancers, but the role of FHL2 in NSCLC angiogenesis has not been intensely examined. Methods FHL2 expression in NSCLC tissues and cell lines and its correlation with patients prognosis were investigated by using The Cancer Genome Atlas (TCGA) database and quantitative polymerase chain reaction (qPCR). Cell Counting Kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, and a xenograft model were used to investigate the effects of FHL2 on NSCLC progression in vitro and in vivo . CCK-8, wound-healing, Transwell invasion, tube formation, and permeability assays were performed to determine the roles of FHL2 in angiogenesis and vascular permeability. Vascular endothelial growth factor A (VEGFA) enzyme-linked immunosorbent assay (ELISA) assay, Western blot analysis, and MK-2206 were used to investigate the specific mechanism mediated by FHL2 . Results We demonstrated that FHL2 was significantly upregulated in NSCLC tissues and cell lines and was associated with poor prognosis. FHL2 overexpression enhanced the cell viability of NSCLC cells, as well as the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, we determined that FHL2 activated the AKT-mTOR signaling pathway in HUVECs by promoting VEGFA secretion from NSCLC cells, thereby inducing angiogenesis and vascular leakiness. We further confirmed that FHL2 also promoted NSCLC tumor growth in vivo . Conclusions Our study revealed the role of FHL2 in NSCLC and the mechanism by which FHL2 promotes NSCLC tumorigenesis, providing novel insights into targeted therapy for NSCLC.

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Section: Discussionmentioning

confidence: 99%

Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability

Chen,

Chen

et al. 2024

J Thorac Dis

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“…Recently, by scRNAseq several studies have identified ECs with a resident endothelial stem cell signature ( 14 – 16 ). However, the definition, cell lineage, and the specific mechanism by which EPCs differentiate into ECs are not yet known ( 40 ). A specific marker to identify EPCs is lacking given that potential typical markers such as CD34, CD31, VEGFR2 and CD133 are shared by vascular ECs and hematopoietic cells (myeloid cells and mesenchymal stem cells) ( 41 ).…”

Section: Endothelial Cells In Tumor Microenvironmentmentioning

confidence: 99%

Endothelial cells in tumor microenvironment: insights and perspectives

Leone,

Malerba,

Susca

et al. 2024

Front. Immunol.

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The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune and endothelial cells (ECs), soluble factors (cytokines, chemokines, and growth factors), blood vessels and extracellular matrix. Within this complex network, ECs are not only relevant for controlling blood fluidity and permeability, and orchestrating tumor angiogenesis but also for regulating the antitumor immune response. Lining the luminal side of vessels, ECs check the passage of molecules into the tumor compartment, regulate cellular transmigration, and interact with both circulating pathogens and innate and adaptive immune cells. Thus, they represent a first-line defense system that participates in immune responses. Tumor-associated ECs are involved in T cell priming, activation, and proliferation by acting as semi-professional antigen presenting cells. Thus, targeting ECs may assist in improving antitumor immune cell functions. Moreover, tumor-associated ECs contribute to the development at the tumor site of tertiary lymphoid structures, which have recently been associated with enhanced response to immune checkpoint inhibitors (ICI). When compared to normal ECs, tumor-associated ECs are abnormal in terms of phenotype, genetic expression profile, and functions. They are characterized by high proliferative potential and the ability to activate immunosuppressive mechanisms that support tumor progression and metastatic dissemination. A complete phenotypic and functional characterization of tumor-associated ECs could be helpful to clarify their complex role within the tumor microenvironment and to identify EC specific drug targets to improve cancer therapy. The emerging therapeutic strategies based on the combination of anti-angiogenic treatments with immunotherapy strategies, including ICI, CAR T cells and bispecific antibodies aim to impact both ECs and immune cells to block angiogenesis and at the same time to increase recruitment and activation of effector cells within the tumor.

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“…Neoangiogenesis provides a new blood supply to tumors, allowing tumor cells to obtain more oxygen and nutrients. It also provides a pathway for tumor cell metastasis using newly formed blood vessels; tumor cells can enter the bloodstream or lymphatic system and spread to distant organs and tissues ( Nowosad et al, 2023 ; Yao and Zeng, 2023 ). Previous studies reported that EVs delivered various bioactive substances (such as miR-29, miR-10a-5p, circ29, and GRP78) to promote the expression of vascular endothelial growth factor (VEGF), thereby promoting angiogenesis ( Zhang et al, 2016 ; Li et al, 2021 ; Zhu et al, 2022d ; Iha et al, 2022 ).…”

Section: Evs Influence Gc Metastasis By Regulating Angiogenesismentioning

confidence: 99%

The biological role of extracellular vesicles in gastric cancer metastasis

Lei,

Cai,

Zhang

et al. 2024

Front. Cell Dev. Biol.

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Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial–mesenchymal transition (EMT) and mesothelial–mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

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Tumour associated endothelial cells: origin, characteristics and role in metastasis and anti-angiogenic resistance

Cited by 16 publications

References 104 publications

Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability

Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability

Endothelial cells in tumor microenvironment: insights and perspectives

The biological role of extracellular vesicles in gastric cancer metastasis

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