Hyaluronan production enhances shedding of plasma membrane-derived microvesicles

• Published in: Experimental cell research 2013-08, Vol.319 (13), p.2006-2018
• Main Authors: Rilla, Kirsi, Pasonen-Seppänen, Sanna, Deen, Ashik J., Koistinen, Ville V.T., Wojciechowski, Sara, Oikari, Sanna, Kärnä, Riikka, Bart, Genevieve, Törrönen, Kari, Tammi, Raija H., Tammi, Markku I.
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; Cell Culture Techniques; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cells, Cultured; Cellular biology; Coated Vesicles - metabolism; Dogs; Enzymes; Extracellular matrix; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Hyaluronan; Hyaluronan synthase; Hyaluronan Synthases; Hyaluronic Acid - metabolism; Hyaluronic Acid - physiology; Male; Membranes; Microvesicle; Plasma; Rats; Rats, Wistar; Transfection
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2013.05.021

Many cell types secrete plasma membrane-bound microvesicles, suggested to play an important role in tissue morphogenesis, wound healing, and cancer spreading. However, the mechanisms of their formation have remained largely unknown. It was found that the tips of long microvilli induced in cells by overexpression of hyaluronan synthase 3 (HAS3) were detach into the culture medium as microvesicles. Moreover, several cell types with naturally active hyaluronan synthesis released high numbers of plasma membrane-derived vesicles, and inhibition of hyaluronan synthesis reduced their formation. The vesicles contained HAS, and were covered with a thick hyaluronan coat, a part of which was retained even after purification with high-speed centrifugation. HAS3 overexpressing MDCK cells cultured in a 3-D matrix as epithelial cysts released large amounts of HAS- and hyaluronan-positive vesicles from their basal surfaces into the extracellular matrix. As far as we know, hyaluronan synthesis is one of the first molecular mechanisms shown to stimulate the production of microvesicles. The microvesicles have a potential to deliver the hyaluronan synthase machinery and membrane and cytoplasmic materials to other cells, influencing tissue regeneration, inflammation and tumor progression. •Hyaluronan synthesis stimulates the shedding of plasma membrane-derived microvesicles.•Hyaluronan-coated vesicles are formed by shedding of the tips of the HAS-induced microvilli.•Vesicles are also shed in 3D cultures and are dependent on active hyaluronan synthesis.•These vesicles offer a potential therapeutic target and a diagnostic tool in cancer.