title: No influence of exogenous hyaluronan on the behavior of human cancer cells or endothelial cell capillary formation.
abstract: Hyaluronan (HA), a type of glycosaminoglycan used to construct the extracellular matrix, is involved in the proliferation and motility of cells, including cancer cells. The aim of this study was to determine whether exogenous HA has an influence on cancer in vitro and in vivo. High-molecular-weight HA (900 kDa) and low-molecular-weight HA (10 kDa) were added to several types of cancer cell lines in vitro, and proliferation and invasion were assessed. The effect of HA on capillary formation by human umbilical vein endothelial cells was also analyzed. The results showed that both types of HA had no apparent effect on cellular proliferation, invasion, or capillary formation. In an animal study, the 2 types of HA were orally administered to tumor-bearing mice at a dosage of 200 mg/kg/d for 4 wk. Analysis using an in vivo imaging system revealed that tumor proliferation and metastasis were not greatly altered by HA administration. Furthermore, CD31 immunohistochemical staining revealed no obvious change in tumor microvessels. Taken together, these results demonstrate that exogenously administered HA has little effect on cancer. This study may support the safety of various forms of HA administration, including oral intake.
  
  
  CONCLUSIONS
  Orally administered hyaluronan was recently found to have beneficial effects. However, the effect of exogenous hyaluronan on cancer remains unclear. Our findings support the safety of orally administered hyaluronan and its use as a functional food ingredient.
authors.affiliation: Div. of Molecular and Cellular Medicine, Natl. Cancer Center Research Inst, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Research & Development Div, Kewpie Corp., 2-5-7, Sengawa-cho, Chofu-shi, Tokyo, 182-0002, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Seino
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.forename: Akira
authors.initials: A
authors.lastname: Asari
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Masuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kunou
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D006820:Hyaluronic Acid
keywords: cancer; food safety; functional food; hyaluronan; polysaccharides