Journal
CLINICAL & EXPERIMENTAL METASTASIS
Volume 28, Issue 2, Pages 113-125Publisher
SPRINGER
DOI: 10.1007/s10585-010-9363-7
Keywords
Extracellular matrix; Versican; Hyaluronan; CD44; Motility; Invasion
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Funding
- University of Adelaide Faculty of Health Sciences
- Ovarian Cancer Research Foundation of Australia
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The assembly of pericellular matrix containing hyaluronan (HA) and versican has been shown to be a prerequisite for proliferation and migration of mesenchymal cells. In this study, we investigated whether treatment with recombinant versican could induce the formation of a pericellular matrix by ovarian cancer cells (OVCAR-3, OVCAR-5, and SKOV-3) and promote their motility, invasion, and adhesion to peritoneal cells in vitro. We also determined whether versican-induced pericellular matrix formation and metastatic cancer cell behavior could be blocked by small HA oligosaccharides. Only combined treatment with recombinant versican and HA resulted in pericellular matrix formation by OVCAR-5 and SKOV-3 but not by OVCAR-3 cells, which lack the HA receptor, CD44. The motility of OVCAR-5 and SKOV-3 cells was significantly increased in scratch wound and chemotaxis assays following treatment with recombinant versican and HA. Versican and HA also promoted invasion of SKOV-3 and OVCAR-5 cells but had no effect on OVCAR-3 cells. We have demonstrated that exogenous HA significantly increased OVCAR-5 and SKOV-3 adhesion to peritoneal cells but adhesion was not further increased by versican treatment. Small HA oligomers (6-10 disaccharides) were able to significantly block formation of pericellular matrix by OVCAR-5 cells, as well as the increased motility and invasion induced by recombinant versican. HA oligomers also significantly blocked OVCAR-5 adhesion to peritoneal cells both in the presence and absence of exogenous HA. The dependence of CD44 for the versican and HA mediated effects were demonstrated by the inhibition of pericellular matrix formation as well as motility and invasion of OVCAR-5 cells following treatment with CD44 neutralizing antibody in the presence of versican and HA. We conclude that the acquisition of a HA/versican pericellular matrix by ovarian cancer cells increases their metastatic potential. HA oligomers can block this mechanism and are promising inhibitors of ovarian cancer dissemination.
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