Hyaluronic acid secreted by mesothelial cells: a natural barrier to ovarian cancer cell adhesion

Abstract

The adhesion to mesothelial monolayers of eight cultured ovarian tumour cell lines was studied in multiwell plates as a model for some of the interactions of ovarian cancer in the peritoneal cavity. When only the upper half of the conditioned medium (CM) from a confluent mesothelial cell culture was aspirated, the adhesion of the tumour cells was low (3.5%-36%). When the medium was removed completely the adhesion increased. The tumour cell lines showing the greatest enhancement of adhesion were those which had previously been shown to express the highest amounts of CD44. By adding erythrocyte suspensions to mesothelial cells it was shown that there was a pericellular coat around the mesothelial cells that could be destroyed by aspirating the medium, or by treating the medium with hyaluronidase (Hase). Treatment of the CM with Hase also considerably increased tumour cell adhesion. Furthermore, CM was shown to contain high amounts of hyaluronic acid (HA). HA blocked adhesion in the absence of CM, but the effect was not as large as that produced by the pericellular coat. It is proposed that pericellular HA produced by mesothelial cells has an important role in the invasion of ovarian tumour cells in the peritoneal cavity.

Hyaluronan-CD44 Interaction with Neural Wiskott-Aldrich Syndrome Protein (N-WASP) Promotes Actin Polymerization and ErbB2 Activation Leading to β-Catenin Nuclear Translocation, Transcriptional Up-regulation, and Cell Migration in Ovarian Tumor Cells

“…HA, a glycosaminoglycan, is present as a loose pericellular layer that coats the mesothelium required for both protection and lubrication within this body cavity (3,4). Overexpression of HA has been found to be associated with ovarian tumor progression (3,4).…”

“…HA, a glycosaminoglycan, is present as a loose pericellular layer that coats the mesothelium required for both protection and lubrication within this body cavity (3,4). Overexpression of HA has been found to be associated with ovarian tumor progression (3,4). HA binds to specific tumor cell-surface receptors such as CD44, which is present in at least 94% of ovarian tumor cells (6,7).…”

Magnetic Resonance Imaging Visualization of Hyaluronidase in Ovarian Carcinoma

“…A significant correlation is found between hyaluronidase activity and metastasis of ovarian cancer (14). Moreover, treatment of conditioned medium with hyaluronidase increases the adhesion of ovarian cancer tumor cells to mesothelial monolayer that serves as a model for metastatic dissemination in the peritoneal cavity (15). Because hyaluronan, hyaluronidase, and CD44 (hyaluronan receptor) are involved in the progression of ovarian carcinoma (16)(17)(18)(19), noninvasive detection of the presence and activity of hyaluronidase may give indication for the process and presence of metastasis.…”

Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells

“…For example, HA levels have been shown to be significantly elevated in the serum of breast cancer patients (11). Also it is believed that tumor cell adhesion to the HA-containing pericellular coat of mesothelial cells is one of the important mechanisms for the peritoneal spread of ovarian cancer (12). HA interacts with a specific cell surface receptor, CD44, which belongs to a family of multifunctional transmembrane glycoproteins expressed in numerous cells and tissues, including breast and ovarian tumor cells and various carcinoma tissues (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”