title: HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells.
abstract: Several studies have suggested that increased production of hyaluronan (HA) is associated with metastatic behavior in various malignant tumors. To our knowledge, HA molecular weights required for metastasis are still unsolved in osteosarcoma. We examined the size of HA and hyaluronan synthase (HAS) isoforms related to biological functions required for metastasis in the LM8 stably highly metastatic osteosarcoma cell line. We found that HA of molecular weight which HAS3 produces enhanced biological functions related to metastasis such as cell proliferation, invasion, and degradation of extracellular matrix. Moreover, cell proliferation and invasion were inhibited by suppressing the activity of HAS3 expressed in LM8 cells, using hyaluronan synthase suppressor, 4-methylumbelliferone (MU). HA with the molecular weight related to HAS2 was the most adherent to CD44 in LM8 cells, suggesting that HAS2 may play an important role in pericellular coat formation. These results suggest that HAS3-related HA enhances crucial biological activities necessary for metastasis and that HAS2-related HA offers an advantageous environment for osteosarcoma cells.
authors.affiliation: Department of Orthopaedic Surgery, Kagoshima Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Tofuku
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yokouchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murayama
authors.forename: Shusaku
authors.initials: S
authors.lastname: Minami
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D006923:Hymecromone / Q000031:analogs & derivatives / Q000494:pharmacology; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D011509:Proteoglycans; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D018960:Hyaluronan Receptors; D007797:Laminin; D011509:Proteoglycans; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C059485:matrigel; D006923:Hymecromone; D006820:Hyaluronic Acid; D003094:Collagen; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2