title: Hypoxia-induced alterations in hyaluronan and hyaluronidase.
abstract: Hyaluronan (HA), a large negatively-charged polysaccharide, is a major component of vessel basal membrane. HA is expressed by a variety of cells, including tumor and endothelial cells. We hypothesized that HA could be up-regulated by hypoxia to enhance vessel formation. To determine the effect of hypoxia on the production of HA, tumor cells were treated with either media alone (control) or a hypoxia inducer (CoCl or NaN3) for 24 h. The level of HA in the media was then measured by ELISA. The results showed that both CoCl and NaN3 induced the production of HA. Since the low molecular weight form of HA (SMW) possesses pro-angiogenic properties, we investigated whether hypoxia-induced HA can be processed into SMW. Under hypoxic conditions, the activity of hyaluronidase, the enzyme responsible for degrading HA, was measured by an ELISA-like assay. The activity of hyaluronidase was shown to be up-regulated by hypoxia and, further, could carry out the function of processing HA into SMW. In addition, the hypoxic areas of tumor tissues were stained strongly with biotinylated HA-binding proteins, indicating that the level of HA was high compared to the oxic areas. This study demonstrates that hypoxia can stimulate the production of HA and the activity of hyaluronidase, which may promote angiogenesis as a compensation mechanism for hypoxia.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.forename: Zeqiu
authors.initials: Z
authors.lastname: Han
authors.forename: Ivan
authors.initials: I
authors.lastname: Ding
authors.forename: Luping
authors.initials: L
authors.lastname: Wang
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhang
authors.forename: Shanmin
authors.initials: S
authors.lastname: Yang
authors.forename: Jinguo
authors.initials: J
authors.lastname: Chen
authors.forename: Charles B
authors.initials: CB
authors.lastname: Underhill
authors.forename: Sunghee
authors.initials: S
authors.lastname: Kim
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051548:Histone Acetyltransferases; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D001619:beta-N-Acetylhexosaminidases
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D006820:Hyaluronic Acid; D051548:Histone Acetyltransferases; C115866:OGA protein, human; D006821:Hyaluronoglucosaminidase; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases