Advanced research on vasculogenic mimicry in cancer

Qiao, Lili; Liang, Ning; Zhang, Jiandong; Xie, Jian; Liu, Fengjun; Xu, Dongjuan; Yu, Xinshuang; Tian, Yuan

doi:10.1111/jcmm.12496

Cited by 188 publications

(243 citation statements)

References 148 publications

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“…[22][23][24] FACS analysis to assess the proportion of CD44 þ /CD24 À CSCs revealed that greater than 90% (94.3% AE 1.8) of the MDA-MB-231 cell population was composed of CSCs; this high proportion of CSCs is a characteristic of basal cell lines. The observation that the majority of cells in the MDA-MB-231 cell line have stem-like properties was in agreement with previous reports.…”

Section: Mda-mb-231 Cells Have a High Proportion Of Cancer Stem Cellsmentioning

confidence: 99%

“…24 Lin et al reported that transgelin downregulation resulted in a reduction in the expression of some EMT markers such as vimentin and fibronectin-1. 13,15,48 Thus, one of the possible mechanisms through which transgelin affects VM is via EMT.…”

Section: Blocking Cxcr2 Receptor Signaling Impairs Proliferation and mentioning

confidence: 99%

“…28 Some of these pathways, such as PI3K/Akt and ERK have been associated with VM. 24 Thus, the inhibition of CXCR2 likely affects VM through these signaling pathways. Additional studies are necessary to elucidate the mechanisms by which IL-8/CXCR2 contributes to tube formation in cancer cells.…”

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confidence: 99%

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Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

Aikins

Kim

Raymundo

et al. 2017

Exp Biol Med (Maywood)

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Vasculogenic mimicry (VM) is an angiogenic-independent mechanism of blood vessel formation whereby aggressive tumor cells undergo formation of capillarylike structures. Thus, interventions aimed at angiogenesis might not target the entire tumor vasculature. A more holistic approach is therefore needed in the development of improved antivascular agents.Transgelin, an actin-binding protein, has been associated with multiple stages of cancer development such as proliferation, migration and invasion, but little is known about its role in vasculogenic mimicry. We present here, an additional mechanism by which transgelin promotes malignancy by way of its association with the occurrence of VM. Although transgelin knockdown did not affect the transcript levels of most of the angiogenesis-related genes in this study, it was associated with the inhibition of the uptake of IL-8, accompanied by suppressed VM, indicating that transgelin is required for VM. These observations are relevant to the future development of efficient antivascular agents. AbstractVasculogenic mimicry (VM) is a non-classical mechanism recently described in many tumors, whereby cancer cells, rather than endothelial cells, form blood vessels. Transgelin is an actin-binding protein that has been implicated in multiple stages of cancer development. In this study, we investigated the role of transgelin in VM and assessed its effect on the expression of endothelial and angiogenesis-related genes during VM in MDA-MB-231 breast cancer cells. We confirmed the ability of MDA-MB-231 cells to undergo VM through a tube formation assay. Flow cytometry analysis revealed an increase in the expression of the endothelial-related markers VE-cadherin and CD34 in cells that underwent VM, compared with those growing in a monolayer, which was confirmed by immunocytochemistry. We employed siRNA to silence transgelin, and knockdown efficiency was determined by western blot analyses. Downregulation of transgelin suppressed cell proliferation and tube formation, but increased IL-8 levels in Matrigel cultures. RT-PCR analyses revealed that the expression of IL-8, VE-cadherin, and CD34 was unaffected by transgelin knockdown, indicating that increased IL-8 expression was not due to enhanced transcriptional activity. More importantly, the inhibition of IL-8/CXCR2 signaling also resulted in suppression of VM with increased IL-8 levels, confirming that increased IL-8 levels after transgelin knockdown was due to inhibition of IL-8 uptake. Our findings indicate that transgelin regulates VM by enhancing IL uptake. These observations are relevant to the future development of efficient antivascular agents.

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Section: Mda-mb-231 Cells Have a High Proportion Of Cancer Stem Cellsmentioning

confidence: 99%

Section: Blocking Cxcr2 Receptor Signaling Impairs Proliferation and mentioning

confidence: 99%

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Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

Aikins

Kim

Raymundo

et al. 2017

Exp Biol Med (Maywood)

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“…The growth and spread of tumors depends on the formation of an adequate vascular support and amoeboid mode of tumor cell invasion (9). Furthermore, several studies have indicated that VEGF serves a role in promoting endothelial cell proliferation and migration, and induces a direct effect on cell proliferation and invasiveness (3,10,11).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

et al. 2018

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Abstract. Primary ovarian cancer is the main cause of gynecological cancer-associated mortality. However, the mechanism behind the spread of ovarian cancer requires elucidation. The present study aimed to investigate the effects of microRNA-126 (miR-126) on differentiation and invasion, and its mechanism in primary ovarian cancer. Ovarian cancer SKOV3 cells transfected with LV3-has-miR-126 mimics and LV3-has-miR-126 inhibitor were produced; it was revealedthatLV-miR-126 mimics could induce cell cycle arrest at G 1 phase, suppress cell invasion through Matrigel-coated membranes and downregulate the expression of vascular endothelial growth factor (VEGF). Furthermore, LV-has-miR-126 inhibitor-transfected cells could increase the number of cells in S phase, induce cell invasion and upregulate the expression of VEGF. The present study, to the best of our knowledge, is the first to report that miR-126 may serve tumor suppressor roles by inducing G 1 cell cycle arrest and suppressing invasion in ovarian cancer cells, at least in part by targeting VEGF expression.

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“…To further increase the therapeutic effect in HCC, miR195, a powerful gene drug inhibiting VEGF, and fasudil, a serine/threonine protein kinase blocking Rho kinase, were simultaneously encapsulated in the same nanoparticles (NPs) in order to suppress VM. [10][11][12][13] The cellular membrane plays the role of a selectively permeable barrier, which also presents a major barrier for intracellular delivery of cargo like plasmid DNA (pDNA), miRNA, small interfering RNA, and drugs. Although the small noncoding RNAs have been extensively studied as novel therapeutics for cancer treatment, large molecular weight, instability in blood circulation, and anionic surface charges have hindered the translation of these RNAs from bench to clinic.…”

Section: Introductionmentioning

confidence: 99%

Aptamer-functionalized peptide H<sub>3</sub>CR<sub>5</sub>C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma

Liu¹,

Wu²,

Gao³

et al. 2016

IJN

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Liver cancer is the fifth most commonly diagnosed malignancy, of which hepatocellular carcinoma (HCC) represents the dominating histological subtype. Antiangiogenic therapy aimed at vascular endothelial growth factor (VEGF) has shown promising but deficient clinical prospects on account of vasculogenic mimicry, a highly patterned vascular channel distinguished from the endothelium-dependent blood vessel, which may function as blood supply networks occurring in aggressive tumors including HCC. In this study, we used a new cationic peptide, disulfide cross-linked stearylated polyarginine peptide modified with histidine (H 3 R 5 ), as a reducible vector, cell penetrating peptide-modified aptamer (ST21) with specific binding to HCC cells to conjugate to peptide H 3 R 5 as the targeting probe, miRNA-195 (miR195) as a powerful gene drug to inhibit VEGF, and fasudil to suppress vasculogenic mimicry by blocking ROCK2, all of which were simultaneously encapsulated in the same nanoparticles. Fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient and miR195 was condensed through electrostatic interaction. ST21-H 3 R 5 -polyethylene glycol (PEG) exhibited excellent loading capacities for both fasudil and miR195 with adjustable dosing ratios. Western blot analysis showed that Fasudil ST21-H 3 R 5 -PEG miR195 had strong silencing activity of ROCK2 and VEGF, as compared with Fasudil H 3 R 5 -PEG miR195 . In vitro and in vivo experiments confirmed that ST21-modified nanoparticles showed significantly higher cellular uptake and therapeutic efficacy in tumor cells or tumor tissues than the unmodified counterparts. These findings suggest that aptamer-conjugated peptide holds great promise for delivering chemical drugs and gene drugs simultaneously to overcome HCC.

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Advanced research on vasculogenic mimicry in cancer

Cited by 188 publications

References 148 publications

Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

Featured Article: Downregulation of transgelin blocks interleukin-8 utilization and suppresses vasculogenic mimicry in breast cancer cells

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

Aptamer-functionalized peptide H<sub>3</sub>CR<sub>5</sub>C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma

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