Author | Hosono, Kozo | en_US |
Author | Nishida, Yoshihiro | en_US |
Author | Knudson, Warren | en_US |
Author | Knudson, Cheryl B. | en_US |
Author | Naruse, Takahiro | en_US |
Author | Suzuki, Yoshitaka | en_US |
Author | Ishiguro, Naoki | en_US |
Date Accessioned | 2011-03-02T15:40:01Z | en_US |
Date Accessioned | 2011-05-17T13:03:50Z | |
Date Available | 2011-03-02T15:40:01Z | en_US |
Date Available | 2011-05-17T13:03:50Z | |
Date of Issue | 2007-07 | en_US |
Identifier (Citation) | American Journal of Pathology; 171:1 p. 274-286 | en_US |
Identifier (URI) | http://hdl.handle.net/10342/3279 | en_US |
Description | Numerous studies have demonstrated a correlation between hyaluronan expression and the malignant properties of various kinds of cancer , and inhibition of hyaluronan production causes decreased tumor growth. Hyaluronan oligosaccharides have been shown to inhibit several tumor cell types via disrup- tion of receptor-hyaluronan interaction. However, few studies have addressed hyaluronan with respect to osteosarcoma. In this study, we examined the ef- fects of exogenously added hyaluronan oligosaccha- rides on tumorigenicity of murine osteosarcoma cells, LM-8, and human osteoblastic osteosarcoma cells, MG-63. Moreover, the critical size of oligomers needed to inhibit malignant properties was defined. Fluorescent hyaluronan oligosaccharides accumu- lated both on the surface of cells and in the cyto- plasm, and this retention was blocked by pretreat- ment with an anti-CD44 monoclonal antibody. Hyaluronan octasaccharides significantly inhibited cell viability and induced apoptosis as defined by cell proliferation and terminal deoxynucleotidyl trans- ferase dUTP nick-end labeling assays, respectively. Octasaccharides also abrogated functional cell-associ- ated matrices and significantly reduced the retention of endogenous hyaluronan. Further, octasaccharide treatment affected an inhibition of cell motility as well as cell invasiveness. Pretreatment of the cells withanti-CD44antibodyreducedtheantitumoreffect of the octasaccharides. In vivo , intratumoral injection of hyaluronan octasaccharides reduced the hyaluronan accumulation in local tumors, resulting in significant suppression of the formation of distant lung metastasis. Together these data suggest that hyaluronan oligosac- charides have potent antitumor effects functioning in part by the abrogation of hyaluronan-rich cell-associated matrices. Originally published American Journal of Pathology, Vol. 171, No. 1, July 2007 | en_US |
Language | en_US | en_US |
Publisher | East Carolina University | en_US |
Related URI | http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6PJN-51PPMKH-Y&_user=10&_coverDate=07%2F31%2F2007&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=562cf0ef8f2f30f0321fc5fea140e3b9&searchtype=a | en_US |
Rights | Author notified of opt-out rights by Cammie Jennings. | en_US |
Subject | Hyaluronan oligosaccharides | en_US |
Subject | Malignant properties | en_US |
Subject | Antitumor effects | en_US |
Title | Hyaluronan Oligosaccharides Inhibit Tumorigenicity of Osteosarcoma Cell Lines MG-63 and LM-8 in Vitro and in Vivo via Perturbation of Hyaluronan-Rich Pericellular Matrix of the Cells | en_US |
Type | Article | en_US |
Identifier (PMID) | PMC1941604 | en_US |
Identifier (DOI) | 10.2353/ajpath.2007.060828 | |
Journal Name | American Journal of Pathology | |
Journal Volume | 171 | |
Journal Issue | 1 | |
Article Pages | 274-286 | |