Expression of hyaluronate and hyaluronate synthase in human primary tumours and their metastases in scid mice

Jojovic, Milan; Delpech, Bertrand; Prehm, Peter; Schumacher, Udo

doi:10.1016/s0304-3835(02)00037-x

Cited by 28 publications

(20 citation statements)

References 19 publications

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“…Dysregulation of HA synthases genes results in abnormal production of HA and promotion of abnormal biological processes such as transformation and metastasis [38]. Thus, it has been observed an elevated expression of HA and HA synthases in peripheral areas of tumors derived from highly breast metastatic cell lines has been detected [39]. Based on these early results, we decided to analyse also specificity the relationship of HA intratumor levels with clinico-pathological parameters in the subgroup of patients with invasive ductal tumor, which represent type the more frequent histological in our field clinical.…”

Section: Discussionmentioning

confidence: 99%

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Corte

González

Lamelas

et al. 2006

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Corte

González

Lamelas

et al. 2006

Breast Cancer Res Treat

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“…Epithelial breast cancer cells HMT3552 [Jojovic et al, 2002], human embryonic kidney cells (HEK) [Hagenfeld et al, 2010], primary human skin fibroblasts cultures from wild type and MRP5 deficient mice have been described. Cells were grown in Dulbecco's medium supplemented with streptomycin/penicillin (100 units of each/ml), 10% fetal calf serum; else they were grown in serum-free Quantum medium supplemented with streptomycin/ penicillin (100 units of each/ml), kanamycin (100 units/ml) on 96-well microtiter plates.…”

Section: Cells and Cell Culturementioning

confidence: 99%

Regulation of cell volume by glycosaminoglycans

Joerges

Schulz

Wegner

et al. 2011

J of Cellular Biochemistry

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Cell volume is regulated by a delicate balance between ion distribution across the plasma membrane and the osmotic properties of intra- and extracellular components. Using a fluorescent calcein indicator, we analysed the effects of glycosaminoglycans on the cell volume of hyaluronan producing fibroblasts and hyaluronan deficient HEK cells over a time period of 30 h. Exogenous glycosaminoglycans induced cell blebbing after 2 min and swelling of fibroblasts to about 110% of untreated cell volume at low concentrations which decreased at higher concentrations. HEK cells did not show cell blebbing and responded by shrinking to 65% of untreated cell volume. Heparin induced swelling of both fibroblasts and HEK cells. Hyaluronidase treatment or inhibition of hyaluronan export led to cell shrinkage indicating that the hyaluronan coat maintained fibroblasts in a swollen state. These observations were explained by the combined action of the Donnan effect and molecular crowding.

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“…Increased HA has been shown to be an independent predictor of ovarian cancer survival. Its levels significantly correlate with the degree of invasiveness and metastatic potential in ovarian cancer tumors [11,21] and it promotes attachment of cancer cells to peritoneal cells via interactions with the HA receptor, CD44 [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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

Ween

Hummitzsch

Rodgers

et al. 2010

Clin Exp Metastasis

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The assembly of pericellular matrix containing hyaluronan (HA) and versican has been shown to be a pre-requisite 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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Expression of hyaluronate and hyaluronate synthase in human primary tumours and their metastases in scid mice

Cited by 28 publications

References 19 publications

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Expression and Clinical Signification of Cytosolic Hyaluronan Levels in Invasive Breast Cancer

Regulation of cell volume by glycosaminoglycans

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

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