Journal
EXPERIMENTAL CELL RESEARCH
Volume 319, Issue 13, Pages 2006-2018Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2013.05.021
Keywords
Microvesicle; Hyaluronan; Hyaluronan synthase; Extracellular matrix
Categories
Funding
- Academy of Finland [131771]
- North Savo Cancer Foundation
- Sigrid Juselius Foundation
- University of Eastern Finland
- Academy of Finland (AKA) [131771, 131771] Funding Source: Academy of Finland (AKA)
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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. (C) 2013 Elsevier Inc. All rights reserved.
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