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Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides

CLINICAL & EXPERIMENTAL METASTASIS (2011)

期刊

CLINICAL & EXPERIMENTAL METASTASIS

卷 28, 期 2, 页码 113-125

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SPRINGER

DOI: 10.1007/s10585-010-9363-7

关键词

Extracellular matrix; Versican; Hyaluronan; CD44; Motility; Invasion

类别

Oncology

资金

University of Adelaide Faculty of Health Sciences
Ovarian Cancer Research Foundation of Australia

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摘要

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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Gelatin-Hyaluronan Click-Crosslinked Cryogels Elucidate Human Macrophage Invasion Behavior

Laura C. Bahlmann, Alexander E. G. Baker, Chang Xue, Sophie Liu, Moritz Meier-Merziger, Danielle Karakas, Luke Zhu, Ileana Co, Spencer Zhao, Allysia Chin, Alison McGuigan, John Kuruvilla, Rob C. Laister, Molly S. Shoichet

Summary: Studies have shown that macrophages migrate to a greater depth in cryogels with greater porosity and pore size, primarily through a matrix metalloproteinase-mediated mechanism. The migration of macrophages in cryogels is influenced by cell polarization, with polarized macrophages using a combination of amoeboid and mesenchymal migration. These findings pave the way for further research on macrophage invasion in a biomimetic tumor microenvironment.

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