Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity

Journal Article · Fri Jul 01 00:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.03.026· OSTI ID:20717622

Nishida, Yoshihiro ^[1]; Knudson, Warren ^[2]; Knudson, Cheryl B ^[2]; Ishiguro, Naoki ^[1]

---

1. Department of Orthopaedic Surgery, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550 (Japan)
2. Department of Biochemistry, Rush Medical College, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612 (United States)

Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.

• OSTI ID: 20717622
• Journal Information: Experimental Cell Research, Vol. 307, Issue 1; Other Information: DOI: 10.1016/j.yexcr.2005.03.026; PII: S0014-4827(05)00152-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL ACCUMULATION
CELL PROLIFERATION
INHIBITION
OLIGONUCLEOTIDES
OSTEOSARCOMAS
POLYMERASE CHAIN REACTION
RETENTION
SKELETON