The role of vascular endothelial cells in tumor metastasis

Yan, Feng; Luo, Senlin; Fan, Dandan; Guo, Xingrong; Ma, Shinan

doi:10.1016/j.acthis.2023.152070

Cited by 8 publications

(5 citation statements)

References 70 publications

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“…It is within such histotypic environments that we were able to appreciate the flow-and cancer cell-driven migration of endothelia into the collagenous stroma, consistent with neoangiogenic morphogenesis seen during cancer invasion [50,51]. Using such a chip we were able to observe the effect of dicarbonyl stress specifically on the efficiency of tumor cell intravasation and found the latter to be higher in methylglyoxal-treated vascular environments compared with untreated controls.…”

Section: Discussionsupporting

confidence: 65%

Dicarbonyl stress enhances tumor intravasation

Kumar,

Samanta,

Jyothsna

et al. 2024

Preprint

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Metastasis of cancer is a multi-step process that involves the migration of transformed cells from their native organ into a vascular channel, followed by their dissemination to prospective sites of colonization. The entry of tumor cells into blood or lymph, known as intravasation involves their breaching the stromal and endothelial extracellular matrix (ECM) and the endothelial barriers. How the kinetics of these cell-ECM interactions are confounded by chronic inflammatory stresses seen in comorbid risk factors of cancer such as diabetes and aging remain ill-investigated. Here, we construct and deploy a histopathology-motivated, imaging-tractable, microfluidic multi-organ-on-chip platform, that seamlessly integrates two tissue environments: that of a breast tumor and a vascular channel, to study the problem. The former comprises invasive triple-negative MDA-MB-231 breast cancer cells embedded within a three-dimensional fibrillar Collagen I milieu. The latter consists of a monolayer of TeloHAEC, immortalized human aortic endothelial cells arranged on laminin-rich basement membrane ECM, both of which concentrically line a hollow channel, wherein unidirectional fluid flows are implemented. The chip showcases the complexity of intravasation, wherein tumor cells and endothelia cooperate to form anastomotic structures. The formation of such structures is regulated by fluid flow in the vascular channel and is associated with cancer cell migration and entry into the vascular channel. Disseminated cancer cells are observed to enter, get adhered within, and flow through the vascular channel. Exposure to methylglyoxal (MG), a mediator of dicarbonyl stress associated with diabetic circulatory milieu, leads to greater cancer cell intravasation and flow through the vascular channel. This could be driven not just by MG-induced endothelial senescence and shedding, but also by the effect of MG on the chip ECM: we demonstrate it can degrade basement membrane and pathologically crosslink Collagen I, diminishing their cell adhesiveness. Our results thus show how dicarbonyl stress may attenuate homoeostatic barriers to cancer intravasation, exacerbating metastasis.

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Section: Discussionsupporting

confidence: 65%

Dicarbonyl stress enhances tumor intravasation

Kumar,

Samanta,

Jyothsna

et al. 2024

Preprint

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“…Alternatively, CAFs in TME also secrete PGE2 to suppress the NK cell function in HCC ( Li et al, 2012 ). Tumor endothelial cells promote tumor angiogenesis and regulate cytotoxic T cells in the TME ( Sakano et al, 2022 ; Feng et al, 2023b ). In HCC, tumor endothelial cells could induce tumor-infiltrating T-cell exhaustion and induce the suppression of tumor growth via silencing glycoprotein non-metastatic melanoma protein B expression ( Sakano et al, 2022 ).…”

Section: Lipid Metabolism In Hccmentioning

confidence: 99%

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

Wang,

Liu,

et al. 2024

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC.

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“…In addition to its effects on cancer and stromal cells, oxidative stress can modulate endothelial cell function, which is suggested by research on the OGG1-NFκB interaction in chromatin [ 62 ]. Dysfunction of the vascular endothelial barrier in cancer has been implicated in disease pathology, progression, and outcome [ 6 , 130 ], as vascular endothelial cells have a key role during tumor metastasis [ 131 ], and the interaction between cancer cell and endothelium has been documented in research models for migration through the blood–brain barrier [ 132 ]. In particular, endothelial–mesenchymal transition has been proposed to occur after anthracycline treatment and to initiate vascular remodeling [ 133 ]; anthracyclines are known triggers of NFκB activation [ 134 ] and specifically initiate endothelial-to-mesenchymal transition [ 135 ] on the one hand, and on the other hand, NFκB activation protects cancer cells from apoptosis [ 136 ].…”

Section: Phenotypic Transitions In the Microenvironmentmentioning

confidence: 99%

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

Vlahopoulos,

Pan,

Varisli

et al. 2023

Cancers

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8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NFκB to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NFκB, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.

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The role of vascular endothelial cells in tumor metastasis

Cited by 8 publications

References 70 publications

Dicarbonyl stress enhances tumor intravasation

Dicarbonyl stress enhances tumor intravasation

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

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