Tumor and Endothelial Cell-Derived Microvesicles Carry Distinct CEACAMs and Influence T-Cell Behavior

Abstract

Normal and malignant cells release a variety of different vesicles into their extracellular environment. The most prominent vesicles are the microvesicles (MVs, 100-1 000 nm in diameter), which are shed of the plasma membrane, and the exosomes (70-120 nm in diameter), derivates of the endosomal system. MVs have been associated with intercellular communication processes and transport numerous proteins, lipids and RNAs. As essential component of immune-escape mechanisms tumor-derived MVs suppress immune responses. Additionally, tumor-derived MVs have been found to promote metastasis, tumor-stroma interactions and angiogenesis. Since members of the carcinoembryonic antigen related cell adhesion molecule (CEACAM)-family have been associated with similar processes, we studied the distribution and function of CEACAMs in MV fractions of different human epithelial tumor cells and of human and murine endothelial cells. Here we demonstrate that in association to their cell surface phenotype, MVs released from different human epithelial tumor cells contain CEACAM1, CEACAM5 and CEACAM6, while human and murine endothelial cells were positive for CEACAM1 only. Furthermore, MVs derived from CEACAM1 transfected CHO cells carried CEACAM1. In terms of their secretion kinetics, we show that MVs are permanently released in low doses, which are extensively increased upon cellular starvation stress. Although CEACAM1 did not transmit signals into MVs it served as ligand for CEACAM expressing cell types. We gained evidence that CEACAM1-positive MVs significantly increase the CD3 and CD3/CD28-induced T-cell proliferation. All together, our data demonstrate that MV-bound forms of CEACAMs play important roles in intercellular communication processes, which can modulate immune response, tumor progression, metastasis and angiogenesis.

Characterization of Endothelial Microparticles Induced by Different Therapeutic Drugs for Infantile Hemangioma

“…Moreover, we observed that the expression percentage of some surface antigens in most EMPs tended to decrease in comparison with that of parental cells, indicating the trend for loss of surface antigens in EMPs from their parental cells. These observations are in accordance with recent studies showing a higher expression of certain surface antigens on parental cells than on MPs released from them, 23,24 which supports the notion that MPs might selectively inherit surface antigens as a special mechanism for conveying information from originating cells to derived MPs.…”

In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments

“…Microvesicles (MVs) are the plasma membrane-derived circular fragments shed from the surface of MSCs and other cell types or released from endosomal compartment (Camussi et al 2010;Muturi et al 2013;Ratajczak 2011). These structures harbor various cell-derived components including surface receptors and ligands, messenger RNAs (mRNAs), microRNAs, proteins, and even some organelles.…”

“…Therefore, these stressors and their effects on stem cells, particularly MSCs, must be identified to maintain MSCs pools or optimize their expansion protocols (Mansouri et al 2012;Tower 2012). In addition, for selective tissue regenerative medicine or preserving MSCs pool, application of some new target tissue-based strategies and modulation of the target tissues to secrete more specific chemokines to facilitate MSCs homing might be possible (Naderi-Meshkin et al 2014).…”

Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

“…IHC and immunocytochemical (ICC) staining was performed according to standard protocols with some modifications (Klein et al, 2011;Muturi et al, 2013). Briefly, ICC cells were grown in glass dishes to appropriate densities, washed with 1· PBS, fixed with 4% formaldehyde in PBS for 20 min, rinsed twice with 1· PBS for 5 min, and blocked with 10% normal goat serum (AbD Serotec) at room temperature for 60 min.…”