title: Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion.
abstract: Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells.
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland. Electronic address: piia.takabe@uef.fi.
authors.forename: Piia
authors.initials: P
authors.lastname: Takabe
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bart
authors.affiliation: University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ropponen
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Rilla
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Tammi
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Tammi
authors.affiliation: University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Pasonen-Seppänen
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Adhesion; Cell cycle; ERK1/2; HAS3; Hyaluronan; Melanoma; Migration; Proliferation