title: Hyaluronan production enhances shedding of plasma membrane-derived microvesicles.
abstract: 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.
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland. Electronic address: kirsi.rilla@uef.fi.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Rilla
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Pasonen-Seppänen
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Ashik J
authors.initials: AJ
authors.lastname: Deen
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Ville V T
authors.initials: VVT
authors.lastname: Koistinen
authors.affiliation: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Sara
authors.initials: S
authors.lastname: Wojciechowski
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Oikari
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Kärnä
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bart
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Törrönen
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Raija H
authors.initials: RH
authors.lastname: Tammi
authors.affiliation: Institutes of Biomedicine, Dentistry, and Biocenter Kuopio and Cancer Center of the University of Eastern Finland, P.O.B. 1627, FIN-70211 Kuopio, Finland.
authors.forename: Markku I
authors.initials: MI
authors.lastname: Tammi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D018699:Coated Vesicles / Q000378:metabolism*; D004285:Dogs; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
chemical_list: D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases
keywords: Biotinylated hyaluronan binding complex; DIC; Differential interference contrast; ELSA; Enzyme-linked sorbent assay; Extracellular matrix; FBS; Fetal bovine serum; Fluorescent hyaluronan binding complex; GFP; Green fluorescent protein; HAS; Hyaluronan; Hyaluronan synthase; Microvesicle; SEM; Scanning electron microscopy; TEM; Transmission electron microscopy; bHABC; fHABC