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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Kozo Hosono (Creator)

Naoki Ishiguro (Creator)

Cheryl B. Knudson (Creator)

Warren Knudson (Creator)

Takahiro Naruse (Creator)

Yoshihiro Nishida (Creator)

Yoshitaka Suzuki (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: 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

Additional Information

Publication

Other

American Journal of Pathology. 171:1(July 2007) p. 274-286.

Language: English

Date: 2011

Keywords

hyaluronan oligosaccharides, malignant properties, antitumor effects

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