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Endothelial and cancer cells interact with mesenchymal stem cells via both microparticles and secreted factors

Lozito, TP and Tuan, RS (2014) Endothelial and cancer cells interact with mesenchymal stem cells via both microparticles and secreted factors. Journal of Cellular and Molecular Medicine, 18 (12). 2372 - 2384. ISSN 1582-1838

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Abstract

Tightly associated with blood vessels in their perivascular niche, human mesenchymal stem cells (MSCs) closely interact with endothelial cells (ECs). MSCs also home to tumours and interact with cancer cells (CCs). Microparticles (MPs) are cell-derived vesicles released into the extracellular environment along with secreted factors. MPs are capable of intercellular signalling and, as biomolecular shuttles, transfer proteins and RNA from one cell to another. Here, we characterize interactions among ECs, CCs and MSCs via MPs and secreted factors in vitro. MPs and non-MP secreted factors (Sup) were isolated from serum-free medium conditioned by human microvascular ECs (HMEC-1) or by the CC line HT1080. Fluorescently labelled MPs were prepared from cells treated with membrane dyes, and cytosolic GFP-containing MPs were isolated from cells transduced with CMV-GFP lentivirus. MSCs were treated with MPs, Sup, or vehicle controls, and analysed for MP uptake, proliferation, migration, activation of intracellular signalling pathways and cytokine release. Fluorescently labelled MPs fused with MSCs, transferring the fluorescent dyes to the MSC surface. GFP was transferred to and retained in MSCs incubated with GFP-MPs, but not free GFP. Thus, only MP-associated cellular proteins were taken up and retained by MSCs, suggesting that MP biomolecules, but not secreted factors, are shuttled to MSCs. MP and Sup treatment significantly increased MSC proliferation, migration, and MMP-1, MMP-3, CCL-2/MCP-1 and IL-6 secretion compared with vehicle controls. MSCs treated with Sup and MPs also exhibited activated NF-κB signalling. Taken together, these results suggest that MPs act to regulate MSC functions through several mechanisms.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lozito, TPtpl9@pitt.eduTPL9
Tuan, RSrst13@pitt.eduRST13
Date: 1 December 2014
Date Type: Publication
Journal or Publication Title: Journal of Cellular and Molecular Medicine
Volume: 18
Number: 12
Page Range: 2372 - 2384
DOI or Unique Handle: 10.1111/jcmm.12391
Schools and Programs: Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1582-1838
Date Deposited: 03 Jul 2017 14:44
Last Modified: 28 Nov 2021 03:55
URI: http://d-scholarship.pitt.edu/id/eprint/32681

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