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

• Published in: Journal of cellular and molecular medicine Vol. 18; no. 12; pp. 2372 - 2384
• Main Authors: Lozito, Thomas P., Tuan, Rocky S.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-12-2014; Blackwell Publishing Ltd
• Subjects: Apoptosis; Behavior; Biomolecules; Blood vessels; Blotting, Western; Cancer; Cell Communication; Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell signaling; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - ultrastructure; Cells, Cultured; Conditioning; Cytokines; Cytokines - secretion; Dyes; Endothelial cells; endothelial cells (ECs); Endothelial Cells - cytology; Endothelial Cells - metabolism; Epidermal growth factor; extracellular vesicles; Fibroblasts; Fluorescent dyes; Fluorescent indicators; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Intracellular signalling; Mesenchymal stem cells; mesenchymal stem cells (MSCs); Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Microparticles; microparticles (MP); Microscopy, Confocal; Microscopy, Electron, Transmission; Microvasculature; Neoplasms - metabolism; Neoplasms - pathology; NF-kappa B - metabolism; Original; perivascular niche; Proteins; Ribonucleic acid; RNA; Signal Transduction; Stem cells; Studies; Time-Lapse Imaging - methods; Tumors; United States > US; perivascular niche; endothelial cells (ECs); extracellular vesicles; mesenchymal stem cells (MSCs); microparticles (MP)
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12391

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.