title: Overexpression of hyaluronan synthase-2 reduces the tumorigenic potential of glioma cells lacking hyaluronidase activity.
abstract: OBJECTIVE
  The interactions of CD44 with hyaluronan are thought to be crucial for tumor cell attachment to the extracellular matrix, migration, and invasion. For migration to occur, however, the interactions between hyaluronan and cell surface receptors need to be transient. Hyaluronidases may facilitate the degradation of hyaluronan bound to the cell surface and thus reduce the interactions of the cells with the matrix, whereas the overproduction of hyaluronan in the absence of hyaluronidase activity may prevent cells from proliferating or invading normal surrounding tissue.
  
  
  METHODS
  We analyzed the effects in vitro and in vivo of hyaluronan synthase-2 (HAS2) overexpression on a murine glioma cell line that is deficient in hyaluronidase activity. In addition, we evaluated the expression levels of HAS and hyaluronidase genes in human glioma cell lines and in glioma specimens.
  
  
  RESULTS
  Increased hyaluronan synthesis had no effect on the in vitro proliferation of the cells but diminished their in vivo growth rate. Several human glioma cell lines were found to overexpress hyaluronan synthases, but they did so in conjunction with hyaluronidase Hyal2 and MGEA5 expression. Similarly, all glioblastomas multiforme expressed hyaluronidases MGEA5 and Hyal2.
  
  
  CONCLUSIONS
  The data suggest that an increased synthesis of hyaluronan by astrocytoma cells is only promoting tumor cell growth in vivo if the cells express hyaluronidases as well.
authors.affiliation: Departments of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Bouchra
authors.initials: B
authors.lastname: Enegd
authors.forename: James A J
authors.initials: JA
authors.lastname: King
authors.forename: Stan
authors.initials: S
authors.lastname: Stylli
authors.forename: Lucy
authors.initials: L
authors.lastname: Paradiso
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kaye
authors.forename: Ulrike
authors.initials: U
authors.lastname: Novak
mesh_terms: D000118:Acetylglucosaminidase; D000818:Animals; D000951:Antigens, Neoplasm; D001254:Astrocytoma / Q000473:pathology / Q000517:prevention & control; D001932:Brain Neoplasms / Q000517:prevention & control; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology; D005910:Glioma / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D014453:Glucuronosyltransferase / Q000494:pharmacology*; D051548:Histone Acetyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D020033:Protein Isoforms / Q000378:metabolism; D012878:Skin Neoplasms / Q000517:prevention & control; D014162:Transfection; D014407:Tumor Cells, Cultured; D001619:beta-N-Acetylhexosaminidases
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D006820:Hyaluronic Acid; D051548:Histone Acetyltransferases; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; C491099:Has2 protein, mouse; D000076002:Hyaluronan Synthases; C115866:OGA protein, human; D006821:Hyaluronoglucosaminidase; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases