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

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.