Dataset Information

Gold Nanoparticles Disrupt Tumor Microenvironment - Endothelial Cell Cross Talk To Inhibit Angiogenic Phenotypes in Vitro.

ABSTRACT: It is currently recognized that perpetual cross talk among key players in tumor microenvironment such as cancer cells (CCs), cancer associated fibroblasts (CAFs), and endothelial cells (ECs) plays a critical role in tumor progression, metastasis, and therapy resistance. Disruption of the cross talk may be useful to improve the outcome of therapeutics for which limited options are available. In the current study we investigate the use of gold nanoparticles (AuNPs) as a therapeutic tool to disrupt the multicellular cross talk within the TME cells with an emphasis on inhibiting angiogenesis. We demonstrate here that AuNPs disrupt signal transduction from TME cells (CCs, CAFs, and ECs) to ECs and inhibit angiogenic phenotypes in vitro. We show that conditioned media (CM) from ovarian CCs, CAFs, or ECs themselves induce tube formation and migration of ECs in vitro. Migration of ECs is also induced when ECs are cocultured with CCs, CAFs, or ECs. In contrast, CM from the cells treated with AuNPs or cocultured cells pretreated with AuNPs demonstrate diminished effects on ECs tube formation and migration. Mechanistically, AuNPs deplete ?95% VEGF165 from VEGF single-protein solution and remove up to ?45% of VEGF165 from CM, which is reflected on reduced activation of VEGF-Receptor 2 (VEGFR2) as compared to control CM. These results demonstrate that AuNPs inhibit angiogenesis via blockade of VEGF-VEGFR2 signaling from TME cells to endothelial cells.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6939887 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gold Nanoparticles Disrupt Tumor Microenvironment - Endothelial Cell Cross Talk To Inhibit Angiogenic Phenotypes in Vitro.

Zhang Yushan Y Xiong Xunhao X Huai Yanyan Y Dey Anindya A Hossen Md Nazir MN Roy Ram Vinod RV Elechalawar Chandra Kumar CK Rao Geeta G Bhattacharya Resham R Mukherjee Priyabrata P

Bioconjugate chemistry 20190522 6

It is currently recognized that perpetual cross talk among key players in tumor microenvironment such as cancer cells (CCs), cancer associated fibroblasts (CAFs), and endothelial cells (ECs) plays a critical role in tumor progression, metastasis, and therapy resistance. Disruption of the cross talk may be useful to improve the outcome of therapeutics for which limited options are available. In the current study we investigate the use of gold nanoparticles (AuNPs) as a therapeutic tool to disrupt ...[more]

PMID: 31067032

Similar Datasets

Project description:Gold nanoparticles (AuNPs) demonstrate clinical potential for drug delivery and imaging diagnostics. As AuNPs aggregate in physiological fluids, polymer-surface modifications are utilized to allow their stabilization and enhance their retention time in blood. However, the impact of AuNPs on blood vessel function remains poorly understood. In the present study, we investigated the effects of AuNPs and their stabilizers on endothelial cell (EC) and vasodilator function.Citrate-stabilized AuNPs (12±3 nm) were synthesized and surface-modified using mercapto polyethylene glycol (mPEG) and polyvinylpyrrolidone (PVP) polymers. Their uptake by isolated ECs and whole vessels was visualized using transmission electron microscopy and quantified using inductively coupled plasma mass spectrometry. Their biological effects on EC proliferation, viability, apoptosis, and the ERK1/2-signaling pathway were determined using automated cell counting, flow cytometry, and Western blotting, respectively. Endothelial-dependent and independent vasodilator functions were assessed using isolated murine aortic vessel rings ex vivo.AuNPs were located in endothelial endosomes within 30 minutes' exposure, while their surface modification delayed this cellular uptake over time. After 24 hours' exposure, all AuNPs (including polymer-modified AuNPs) induced apoptosis and decreased cell viability/proliferation. These inhibitory effects were lost after 48 hours' exposure (except for the PVP-modified AuNPs). Furthermore, all AuNPs decreased acetylcholine (ACh)-induced phosphorylation of ERK1/2, a key signaling protein of cell function. mPEG-modified AuNPs had lower cytostatic effects than PVP-modified AuNPs. Citrate-stabilized AuNPs did not alter endothelial-dependent vasodilation induced by ACh, but attenuated endothelial-independent responses induced by sodium nitroprusside. PVP-modified AuNPs attenuated ACh-induced dilation, whereas mPEG-modified AuNPs did not, though this was dose-related.We demonstrated that mPEG-modified AuNPs at a therapeutic dosage showed lower cytostatic effects and were less detrimental to vasodilator function than PVP-modified AuNPs, indicating greater potential as agents for diagnostic imaging and therapy.

Dataset Information

Gold Nanoparticles Disrupt Tumor Microenvironment - Endothelial Cell Cross Talk To Inhibit Angiogenic Phenotypes in Vitro.

Publications

Gold Nanoparticles Disrupt Tumor Microenvironment - Endothelial Cell Cross Talk To Inhibit Angiogenic Phenotypes in Vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets